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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.
International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.
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Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.
International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.
Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.
Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.
Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.
An International Open Access Journal Devoted to General Medicine.
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Li MJ, Liu HY, Zhang YQ, Li SR, Zhang JH and Li R: Global burden of chronic kidney disease and its attributable risk factors (1990-2021): An analysis based on the global burden of disease study. Front Endocrinol (Lausanne). 16:15632462025. View Article : Google Scholar : PubMed/NCBI | |
|
de Sa JR, Rangel EB, Canani LH, Bauer AC, Escott GM, Zelmanovitz T, Bertoluci MC and Silveiro SP: The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: An evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD. Diabetol Metab Syndr. 14:812022. View Article : Google Scholar : PubMed/NCBI | |
|
Sanghavi SF, Roark T, Zelnick LR, Najafian B, Andeen NK, Alpers CE, Pichler R, Ayers E and de Boer IH: Histopathologic and clinical features in patients with diabetes and kidney disease. Kidney360. 1:1217–1225. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Barutta F, Bellini S and Gruden G: Mechanisms of podocyte injury and implications for diabetic nephropathy. Clin Sci (Lond). 136:493–520. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang M, Huang Z, Li X, He P, Sun H, Peng Y and Fan Q: Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis. Pharmacol Res. 207:1073062024. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Q, Xie C, Tang K, Luo M, Zhang Z, Jin Y, Liu Y, Zhou L and Kong Y: The E3 ligase Trim63 promotes podocyte injury and proteinuria by targeting PPARalpha to inhibit fatty acid oxidation. Free Radic Biol Med. 209:40–54. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Song S, Hu T, Shi X, Jin Y, Liu S, Li X, Zou W and Wang C: ER Stress-perturbed intracellular protein O-GlcNAcylation aggravates podocyte injury in diabetes nephropathy. Int J Mol Sci. 24:176032023. View Article : Google Scholar : PubMed/NCBI | |
|
He M, Wang Z, Miao Z, Zhao Y, Wei L, Zhang L, Yin R, Wang Y and Yang L: Post-translational modifications in diabetic kidney disease (Review). Int J Mol Med. 57:882026. View Article : Google Scholar | |
|
Gu W, Wang X, Zhao H, Geng J, Li X, Zheng K, Guan Y, Hou X, Wang C and Song G: Resveratrol ameliorates diabetic kidney injury by reducing lipotoxicity and modulates expression of components of the junctional adhesion molecule-like/sirtuin 1 lipid metabolism pathway. Eur J Pharmacol. 918:1747762022. View Article : Google Scholar : PubMed/NCBI | |
|
Qi B, Chen Y, Chai S, Lu X and Kang L: O-linked beta-N-acetylglucosamine (O-GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy. Diabet Med. 42:e154362025. View Article : Google Scholar | |
|
Zhu W, Guo S, Sun J, Zhao Y and Liu C: Lactate and lactylation in cardiovascular diseases: current progress and future perspectives. Metabolism. 158:1559572024. View Article : Google Scholar : PubMed/NCBI | |
|
Xu B, Liu Y, Li N and Geng Q: Lactate and lactylation in macrophage metabolic reprogramming: Current progress and outstanding issues. Front Immunol. 15:13957862024. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang JX, Wang Z and Yu T: Lactate metabolism in human health and disease. Signal Transduct Target Ther. 7:3052022. View Article : Google Scholar : PubMed/NCBI | |
|
Warburg O, Wind F and Negelein E: The metabolism of tumors in the body. J Gen Physiol. 8:519–530. 1927. View Article : Google Scholar : PubMed/NCBI | |
|
Dimitriadis GD, Maratou E, Kountouri A, Board M and Lambadiari V: Regulation of postabsorptive and post-prandial glucose metabolism by Insulin-Dependent and Insulin-independent mechanisms: An Integrative Approach. Nutrients. 13:1592021. View Article : Google Scholar | |
|
Lee DY, Kim JY, Ahn E, Hyeon JS, Kim GH, Park KJ, Jung Y, Lee YJ, Son MK, Kim SW, et al: Associations between local acidosis induced by renal LDHA and renal fibrosis and mitochondrial abnormalities in patients with diabetic kidney disease. Transl Res. 249:88–109. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Darshi M, Kugathasan L, Maity S, Sridhar VS, Fernandez R, Limonte CP, Grajeda BI, Saliba A, Zhang G, Drel VR, et al: Glycolytic lactate in diabetic kidney disease. JCI Insight. 9:e1688252024. View Article : Google Scholar : PubMed/NCBI | |
|
Azushima K, Kovalik JP, Yamaji T, Ching J, Chng TW, Guo J, Liu JJ, Nguyen M, Sakban RB, George SE, et al: Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathy. Kidney Int. 104:1135–1149. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Kugathasan L, Darshi M, Srinivasan Sridhar V, Drel V, Tumova J, Liu JJ, Wang J, Perkins BA, Lytvyn Y, Natarajan L, et al: 12-OR: Urine lactate is a disease biomarker for diabetic kidney disease. Diabetes. 72:12–OR. 2023. View Article : Google Scholar | |
|
Chen Y, Liu X, Shengbu M, Shi Q, Jiaqiu S and Lai X: Biomarkers: New advances in diabetic nephropathy. Natural Product Communications. 20:1934578X2513217582025. View Article : Google Scholar | |
|
Xu Y, Li X, Mao Z and Xue C: Protein lactylation in kidney diseases. Front Cell Dev Biol. 13:15331752025. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng Y and Guo L: Lactate metabolism and lactylation in kidney diseases: Insights into mechanisms and therapeutic opportunities. Ren Fail. 47:24697462025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou M, Liu L, Sun Y and Wang X: Lactylation in diabetes mellitus and its complications: Mechanisms of action and therapeutic potential-recent advances. Front Endocrinol (Lausanne). 16:17106452025. View Article : Google Scholar | |
|
Wei X, Long M, Yu J and Du Y: The lactate-lactylation axis in renal fibrosis: Potential mechanisms in diabetic kidney disease. Ann Med. 57:25873262025. View Article : Google Scholar : PubMed/NCBI | |
|
Gao M, Wang M, Zhou S, Hou J, He W, Shu Y and Wang X: Machine learning-based prognostic model of lactylation-related genes for predicting prognosis and immune infiltration in patients with lung adenocarcinoma. Cancer Cell Int. 24:4002024. View Article : Google Scholar : PubMed/NCBI | |
|
Fu C, Jia Z, Fu Y, Zhang Y, Wu Y, Cao X, Cao D and Jiang J: The clinical prognostic value of lactylation-regulated proteins in gastric cancer. J Proteome Res. 25:446–459. 2026. View Article : Google Scholar : | |
|
Yang X, Li G, Jiang R, Yang Y, Zhu H, Huang L, Li T, Zhou J and Liu Z: Lactylation-related gene signatures for prognosis and treatment response prediction in radiation-resistant non-small cell lung cancer. Discover Oncol. 16:17872025. View Article : Google Scholar | |
|
Wu Q, Qiu X and Chen H: Advancements in early biomarkers of acute kidney injury: From traditional indicators to a paradigm shift in lactate metabolism. Ann Med. 58:26123832026. View Article : Google Scholar : PubMed/NCBI | |
|
Concepción M, Quiroz J, Suarez J, Paz J, Roseboom P, Ildefonso S, Cribilleros D, Zavaleta F, Coronado J and Concepción L: Novel Biomarkers for the diagnosis of diabetic nephropathy. Caspian J Intern Med. 15:382–391. 2024.PubMed/NCBI | |
|
Cai D, Yuan X, Cai DQ, Li A, Yang S, Yang W, Duan J, Zhuo W, Min J, Peng L and Wei J: Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma. J Cancer Res Clin Oncol. 149:11517–11530. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Kemp E, Jacobsen IA and Amtrup F: LDH release into perfusates of preserved kidneys. Scand J Urol Nephrol. 10:142–146. 1976. View Article : Google Scholar : PubMed/NCBI | |
|
Valvona CJ, Fillmore HL, Nunn PB and Pilkington GJ: The regulation and function of lactate dehydrogenase a: Therapeutic potential in brain tumor. Brain Pathol. 26:3–17. 2016. View Article : Google Scholar | |
|
Osis G, Traylor AM, Black LM, Spangler D, George JF, Zarjou A, Verlander JW and Agarwal A: Expression of lactate dehydrogenase A and B isoforms in the mouse kidney. Am J Physiol Renal Physiol. 320:F706–F718. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Brooks GA: Cell-cell and intracellular lactate shuttles. J Physiol. 587:5591–5600. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Becker HM, Klier M and Deitmer JW: Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II. J Membr Biol. 234:125–135. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Iwanaga T and Kishimoto A: Cellular distributions of monocarboxylate transporters: A review. Biomed Res. 36:279–301. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Halestrap AP: Monocarboxylic acid transport. Compr Physiol. 3:1611–1643. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Becker HM, Mohebbi N, Perna A, Ganapathy V, Capasso G and Wagner CA: Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis. Am J Physiol Renal Physiol. 299:F141–F154. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Thangaraju M, Ananth S, Martin PM, Roon P, Smith SB, Sterneck E, Prasad PD and Ganapathy V: c/ebpdelta Null mouse as a model for the double knock-out of slc5a8 and slc5a12 in kidney. J Biol Chem. 281:26769–26773. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Py G, Lambert K, Perez-Martin A, Raynaud E, Prefaut C and Mercier J: Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats. Am J Physiol Endocrinol Metab. 281:E1308–F1315. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Py G, Lambert K, Milhavet O, Eydoux N, Prefaut C and Mercier J: Effects of streptozotocin-induced diabetes on markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters. Metabolism. 51:807–813. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Enoki T, Yoshida Y, Hatta H and Bonen A: Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats. J Appl Physiol (1985). 94:2433–2438. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Ahmed K, Tunaru S and Offermanns S: GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci. 30:557–562. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Hoque R, Farooq A, Ghani A, Gorelick F and Mehal WZ: Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology. 146:1763–1774. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jones NK, Stewart K, Czopek A, Menzies RI, Thomson A, Moran CM, Cairns C, Conway BR, Denby L, Livingstone DEW, et al: Endothelin-1 mediates the systemic and renal hemodynamic effects of GPR81 activation. Hypertension. 75:1213–1222. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Brown TP and Ganapathy V: Lactate/GPR81 signaling and proton motive force in cancer: Role in angiogenesis, immune escape, nutrition, and Warburg phenomenon. Pharmacol Ther. 206:1074512020. View Article : Google Scholar | |
|
Yang K, Xu J, Fan M, Tu F, Wang X, Ha T, Williams DL and Li C: Lactate suppresses macrophage pro-inflammatory response to LPS stimulation by inhibition of YAP and NF-κB Activation via GPR81-mediated signaling. Front Immunol. 11:5879132020. View Article : Google Scholar | |
|
Ranganathan P, Shanmugam A, Swafford D, Suryawanshi A, Bhattacharjee P, Hussein MS, Koni PA, Prasad PD, Kurago ZB, Thangaraju M, et al: GPR81, a Cell-surface receptor for lactate, regulates intestinal homeostasis and protects mice from experimental colitis. J Immunol. 200:1781–1789. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Llibre A, Kucuk S, Gope A, Certo M and Mauro C: Lactate: A key regulator of the immune response. Immunity. 58:535–554. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Guo S, Ye M, Zhu W and Liu C: From fuel to epigenetic signal: Lactate-lactylation axis orchestrates diabetic complications. Pharmacol Res. 222:1080522025. View Article : Google Scholar : PubMed/NCBI | |
|
Liu J, Zhao F and Qu Y: Lactylation: A novel post-translational modification with clinical implications in CNS diseases. Biomolecules. 14:11752024. View Article : Google Scholar : PubMed/NCBI | |
|
Ishihara S, Hata K, Hirose K, Okui T, Toyosawa S, Uzawa N, Nishimura R and Yoneda T: The lactate sensor GPR81 regulates glycolysis and tumor growth of breast cancer. Sci Rep. 12:62612022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen S, Zhou L, Sun J, Qu Y and Chen M: The role of cAMP-PKA pathway in Lactate-induced intramuscular triglyceride accumulation and mitochondria content increase in mice. Front Physiol. 12:7091352021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Yang M, Liu X, Fan J and Wang C: G protein-coupled receptor-mediated renal fibrosis: A key focus on kidney disease drug development. Front Pharmacol. 16:16458882025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhi Y, Fan K, Liu S, Hu K, Zan X, Lin L, Yang Y, Gong X, Chen K, Tang L, et al: Deletion of GPR81 activates CREB/Smad7 pathway and alleviates liver fibrosis in mice. Mol Med. 30:992024. View Article : Google Scholar : PubMed/NCBI | |
|
Wu X, Xu M, Geng M, Chen S, Little PJ, Xu S and Weng J: Targeting protein modifications in metabolic diseases: Molecular mechanisms and targeted therapies. Signal Transduct Target Ther. 8:2202023. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Y, Guo X, Hu X, Zhou S, Yang Q, Feng P and Zeng L: Lysine lactylation in diseases: Beyond histone lactylation. Cell Death Dis. 17:552025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic regulation of gene expression by histone lactylation. Nature. 574:575–580. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Moreno-Yruela C, Zhang D, Wei W, Bæk M, Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, et al: Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 8:eabi66962022. View Article : Google Scholar : PubMed/NCBI | |
|
Cui H, Xie N, Banerjee S, Ge J, Jiang D, Dey T, Matthews QL, Liu RM and Liu G: Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation. Am J Respir Cell Mol Biol. 64:115–125. 2021. View Article : Google Scholar | |
|
Xie B, Zhang M, Li J, Cui J, Zhang P, Liu F, Wu Y, Deng W, Ma J, Li X, et al: KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc Natl Acad Sci USA. 121:e23141281212024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang N, Wang W, Wang X, Mang G, Chen J, Yan X, Tong Z, Yang Q, Wang M, Chen L, et al: Histone lactylation boosts reparative gene activation post-myocardial infarction. Circ Res. 131:893–908. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Dong H, Zhang J, Zhang H, Han Y, Lu C, Chen C, Tan X, Wang S, Bai X, Zhai G, et al: YiaC and CobB regulate lysine lactylation in Escherichia coli. Nat Commun. 13:66282022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Wang Z, Wang Q, Li X and Guo Y: Ubiquitous protein lactylation in health and diseases. Cell Mol Biol Lett. 29:232024. View Article : Google Scholar : PubMed/NCBI | |
|
Zong Z, Ren J, Yang B, Zhang L and Zhou F: Emerging roles of lysine lactyltransferases and lactylation. Nat Cell Biol. 27:563–574. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Gaffney DO, Jennings EQ, Anderson CC, Marentette JO, Shi T, Schou Oxvig AM, Streeter MD, Johannsen M, Spiegel DA, Chapman E, et al: Non-enzymatic Lysine lactoylation of glycolytic enzymes. Cell Chem Biol. 27:206–213.e6. 2020. View Article : Google Scholar | |
|
Chen X, Yuan Y, Zhou F, Li L, Pu J, Zeng Y and Jiang X: Lactylation: From homeostasis to pathological implications and therapeutic strategies. MedComm (2020). 6:e702262025. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng T, Gu YP, Wang JM, Huang TT, Gou LS and Liu YW: Lactate-triggered histone lactylation contributes to podocyte epithelial-mesenchymal transition in diabetic nephropathy in mice. Chem Biol Interact. 408:1114182025. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Liu C, Li R, Zhou L, Ran Y, Yang Q, Huang H, Lu H, Song H, Yang B, et al: AARS1 and AARS2 sense L-lactate to regulate cGAS as global lysine lactyltransferases. Nature. 634:1229–1237. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Che X, Zhang Y, Chen X, Xie G, Li J, Xu C, Zhang C, Zhu Y and Yang X: The lactylation-macrophage interplay: Implications for gastrointestinal disease therapeutics. Front Immunol. 16:16081152025. View Article : Google Scholar : PubMed/NCBI | |
|
Wan L, Zhang H, Liu J, He Q, Zhao J, Pan C, Zheng K and Tang Y: Lactylation and human disease. Expert Rev Mol Med. 27:e102025. View Article : Google Scholar : PubMed/NCBI | |
|
Lu Z, Zheng X, Shi M, Yin Y, Liang Y, Zou Z, Ding C, He Y, Zhou Y and Li X: Lactylation: The emerging frontier in post-translational modification. Front Genet. 15:14232132024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang T, Ye Z, Li Z, Jing DS, Fan GX, Liu MQ, Zhuo QF, Ji SR, Yu XJ, Xu XW and Qin Y: Lactate-induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer. Cell Prolif. 56:e134782023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao L, Qi H, Lv H, Liu W, Zhang R and Yang A: Lactylation in health and disease: Physiological or pathological? Theranostics. 15:1787–1821. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Chen J, Feng Q, Qiao Y, Pan S, Liang L, Liu Y, Zhang X, Liu D and Liu Z and Liu Z: ACSF2 and lysine lactylation contribute to renal tubule injury in diabetes. Diabetologia. 67:1429–1443. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Hong J, Xu H, Yu L, Yu Z, Chen X, Meng Z, Zhu J, Li J and Zhu M: AARS1-mediated lactylation of H3K18 and STAT1 promotes ferroptosis in diabetic nephropathy. Cell Death Differ. Sep 23–2025. View Article : Google Scholar : Epub ahead of print. PubMed/NCBI | |
|
Zhang X, Chen J, Lin R, Huang Y, Wang Z, Xu S, Wang L, Chen F, Zhang J, Pan K and Yin Z: Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway. Redox Biol. 75:1032462024. View Article : Google Scholar : PubMed/NCBI | |
|
Qian J, Huang C, Wang M, Liu Y, Zhao Y, Li M, Zhang X, Gao X, Zhang Y, Wang Y, et al: Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment. Redox Biol. 71:1031032024. View Article : Google Scholar : PubMed/NCBI | |
|
Song M, Liu B, Wang H and Sun W: Lactate metabolism and lactylation modification: New opportunities and challenges in cardiovascular disease. MedComm (2020). 6:e702692025. View Article : Google Scholar : PubMed/NCBI | |
|
Peng X and Du J: Histone and non-histone lactylation: Molecular mechanisms, biological functions, diseases, and therapeutic targets. Mol Biomed. 6:382025. View Article : Google Scholar : PubMed/NCBI | |
|
Tessarz P and Kouzarides T: Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 15:703–708. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Dai W, Wu G, Liu K, Chen Q, Tao J, Liu H and Shen M: Lactate promotes myogenesis via activating H3K9 lactylation-dependent up-regulation of Neu2 expression. J Cachexia Sarcopenia Muscle. 14:2851–2865. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Sun T, Zhang JN, Lan T, Shi L, Hu L, Yan L, Wei C, Hei L, Wu W, Luo Z, et al: H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke. Cell Death Dis. 16:5532025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Yang Y, Chen X, Chen H, Kuang E, Deng M and Wang F: Histone lactylation dynamics are associated with impaired maternal-to-zygotic transition in vitro-cultured goat embryos. Theriogenology. 256:1178592026. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang Z, Xiong N, Yan R, Li ST, Liu H, Mao Q, Sun Y, Shen S, Ye L, Gao P, et al: PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression. Protein Cell. 16:49–63. 2025. View Article : Google Scholar : | |
|
Yang Y, Wen J, Lou S, Han Y, Pan Y, Zhong Y, He Q, Zhang Y, Mo X, Ma J and Shen N: DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation. J Mol Cell Biol. 16:mjae0562025. View Article : Google Scholar : | |
|
Guan B, Zhou M, Dai W, Zhang J, Xie B, Mi Y, Zhang X, Wei P, Liu Y, Li S, et al: Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation. Nat Aging. 5:2449–2465. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Y, Song L, Yu L, Zhang J and Zhang B: H4K12 lactylation potentiates mitochondrial oxidative stress via the Foxo1 pathway in diabetes-induced cognitive impairment. J Adv Res. 78:391–407. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Jiao Q, Ren Y, Teng X, Feng M, Liu X, Cai Y, Hu T, Wang M and Wang Y: Positive feedback between histone H4K16 lactylation and glycolysis promotes MAFLD progression. Hepatol Int. Dec 2–2025. View Article : Google Scholar : Epub ahead of print. PubMed/NCBI | |
|
Galle E, Wong CW, Ghosh A, Desgeorges T, Melrose K, Hinte LC, Castellano-Castillo D, Engl M, de Sousa JA, Ruiz-Ojeda FJ, et al: H3K18 lactylation marks tissue-specific active enhancers. Genome Biol. 23:2072022. View Article : Google Scholar : PubMed/NCBI | |
|
Pan L, Feng F, Wu J, Fan S, Han J, Wang S, Yang L, Liu W, Wang C and Xu K: Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol Res. 181:1062702022. View Article : Google Scholar : PubMed/NCBI | |
|
Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, Liao Y, Yan Y, Li Q, Zhou X, et al: Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease. Cell Metab. 34:634–648.e6. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen J, He J, Wang X, Bai L, Yang X, Chen J, He Y and Chen K: Glis1 inhibits RTEC cellular senescence and renal fibrosis by downregulating histone lactylation in DKD. Life Sci. 361:1232932025. View Article : Google Scholar | |
|
Gao M, Zhang N and Liang W: Systematic analysis of lysine lactylation in the plant fungal pathogen botrytis cinerea. Front Microbiol. 11:5947432020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao W, Yu H, Liu X, Wang T, Yao Y, Zhou Q, Zheng X and Tan F: Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii. Parasit Vectors. 15:1802022. View Article : Google Scholar : PubMed/NCBI | |
|
Dong H, Sun Y, Nie L, Cui A, Zhao P, Leung WK and Wang Q: Metabolic memory: Mechanisms and diseases. Signal Transduct Target Ther. 9:382024. View Article : Google Scholar : PubMed/NCBI | |
|
Erekat NS: Programmed cell death in diabetic nephropathy: A review of apoptosis, autophagy, and necroptosis. Med Sci Monit. 28:e9377662022. View Article : Google Scholar : PubMed/NCBI | |
|
Yu H, Zhu T, Ma D, Cheng X, Wang S and Yao Y: The role of nonhistone lactylation in disease. Heliyon. 10:e362962024. View Article : Google Scholar : PubMed/NCBI | |
|
Tang S, Sun Y, Sun W, Kang X, Zhao X, Jiang L, Gao Q, An X, Ji H and Lian F: Programmed cell death in diabetic kidney disease: Mechanisms and therapeutic targeting. J Inflamm Res. 18:13001–13037. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Watkins PA, Maiguel D, Jia Z and Pevsner J: Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res. 48:2736–2750. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Perera RJ, Marcusson EG, Koo S, Kang X, Kim Y, White N and Dean NM: Identification of novel PPARgamma target genes in primary human adipocytes. Gene. 369:90–99. 2006. View Article : Google Scholar | |
|
Wiese EK, Hitosugi S, Loa ST, Sreedhar A, Andres-Beck LG, Kurmi K, Pang YP, Karnitz LM, Gonsalves WI and Hitosugi T: Enzymatic activation of pyruvate kinase increases cytosolic oxaloacetate to inhibit the Warburg effect. Nat Metab. 3:954–968. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MAR, Sheedy FJ, Gleeson LE, van den Bosch MWM, Quinn SR, Domingo-Fernandez R, Johnston DGW, et al: Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 21:3472015. View Article : Google Scholar | |
|
Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK and Lu Z: PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell. 150:685–696. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, et al: Digoxin suppresses pyruvate kinase M2-promoted HIF-1α transactivation in steatohepatitis. Cell Metab. 27:11562018. View Article : Google Scholar | |
|
Kocak MZ, Aktas G, Atak BM, Duman TT, Yis OM, Erkus E and Savli H: Is Neuregulin-4 a predictive marker of microvascular complications in type 2 diabetes mellitus? Eur J Clin Invest. 50:e132062020. View Article : Google Scholar : PubMed/NCBI | |
|
Amdur RL, Feldman HI, Gupta J, Yang W, Kanetsky P, Shlipak M, Rahman M, Lash JP, Townsend RR, Ojo A, et al: Inflammation and progression of CKD: The CRIC study. Clin J Am Soc Nephrol. 11:1546–1556. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Qi W, Keenan HA, Li Q, Ishikado A, Kannt A, Sadowski T, Yorek MA, Wu IH, Lockhart S, Coppey LJ, et al: Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction. Nat Med. 23:753–762. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Li L, Tang L, Yang X, Chen R, Zhang Z, Leng Y and Chen AF: Gene regulatory effect of pyruvate kinase M2 is involved in renal inflammation in type 2 diabetic nephropathy. Exp Clin Endocrinol Diabetes. 128:599–606. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Gordin D, Shah H, Shinjo T, St-Louis R, Qi W, Park K, Paniagua SM, Pober DM, Wu IH, Bahnam V, et al: Characterization of glycolytic enzymes and pyruvate kinase M2 in type 1 and 2 diabetic nephropathy. Diabetes Care. 42:1263–1273. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Liu H, Takagaki Y, Kumagai A, Kanasaki K and Koya D: The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1alpha accumulation. J Diabetes Investig. 12:697–709. 2021. View Article : Google Scholar : | |
|
Zhang Z, Deng X, Liu Y, Liu Y, Sun L and Chen F: Correction to: PKM2, function and expression and regulation. Cell Biosci. 9:592019. View Article : Google Scholar : PubMed/NCBI | |
|
Angiari S, Runtsch MC, Sutton CE, Palsson-McDermott EM, Kelly B, Rana N, Kane H, Papadopoulou G, Pearce EL, Mills KHG, et al: Pharmacological activation of pyruvate kinase M2 inhibits CD4+ T cell pathogenicity and suppresses autoimmunity. Cell Metab. 31:391–405.e8. 2020. View Article : Google Scholar | |
|
Sweetwyne MT, Gruenwald A, Niranjan T, Nishinakamura R, Strobl LJ and Susztak K: Notch1 and Notch2 in podocytes play differential roles during diabetic nephropathy development. Diabetes. 64:4099–4111. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Yokoyama M, Tanuma N, Shibuya R, Shiroki T, Abue M, Yamamoto K, Miura K, Yamaguchi K, Sato I, Tamai K and Satoh K: Pyruvate kinase type M2 contributes to the development of pancreatic ductal adenocarcinoma by regulating the production of metabolites and reactive oxygen species. Int J Oncol. 52:881–891. 2018.PubMed/NCBI | |
|
Zheng S, Liu Q, Liu T and Lu X: Posttranslational modification of pyruvate kinase type M2 (PKM2): Novel regulation of its biological roles to be further discovered. J Physiol Biochem. 77:355–363. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Prakasam G, Iqbal MA, Bamezai RNK and Mazurek S: Posttranslational modifications of pyruvate kinase M2: Tweaks that benefit cancer. Front Oncol. 8:222018. View Article : Google Scholar : PubMed/NCBI | |
|
Coassolo S, Davidson G, Negroni L, Gambi G, Daujat S, Romier C and Davidson I: Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. Nat Commun. 12:17182021. View Article : Google Scholar : PubMed/NCBI | |
|
Xia L, Jiang Y, Zhang XH, Wang XR, Wei R, Qin K and Lu Y: SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells. Cell Death Dis. 12:1012021. View Article : Google Scholar : PubMed/NCBI | |
|
Das Gupta K, Shakespear MR, Curson JEB, Murthy AMV, Iyer A, Hodson MP, Ramnath D, Tillu VA, von Pein JB, Reid RC, et al: Class IIa histone deacetylases drive Toll-like receptor-inducible glycolysis and macrophage inflammatory responses via pyruvate kinase M2. Cell Rep. 30:2712–2728.e8. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, et al: O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene. 39:560–573. 2020. View Article : Google Scholar : | |
|
Wang J, Yang P, Yu T, Gao M, Liu D, Zhang J, Lu C, Chen X, Zhang X and Liu Y: Lactylation of PKM2 suppresses inflammatory metabolic adaptation in Pro-inflammatory macrophages. Int J Biol Sci. 18:6210–6225. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Sosa RA, Terry AQ, Kaldas FM, Jin YP, Rossetti M, Ito T, Li F, Ahn RS, Naini BV, Groysberg VM, et al: Disulfide High-mobility group box 1 drives ischemia-reperfusion injury in human liver transplantation. Hepatology. 73:1158–1175. 2021. View Article : Google Scholar | |
|
Chen R, Kang R and Tang D: The mechanism of HMGB1 secretion and release. Exp Mol Med. 54:91–102. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Yang H, Zeng Q, Silverman HA, Gunasekaran M, George SJ, Devarajan A, Addorisio ME, Li J, Tsaava T, Shah V, et al: HMGB1 released from nociceptors mediates inflammation. Proc Natl Acad Sci USA. 118:e21020341182021. View Article : Google Scholar : PubMed/NCBI | |
|
Venereau E, Casalgrandi M, Schiraldi M, Antoine DJ, Cattaneo A, De Marchis F, Liu J, Antonelli A, Preti A, Raeli L, et al: Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med. 209:1519–1528. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Tang D, Kang R, Livesey KM, Kroemer G, Billiar TR, Van Houten B, Zeh HJ III and Lotze MT: High-mobility group box 1 is essential for mitochondrial quality control. Cell Metab. 13:701–711. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, Sohn JW, Yamada S, Maruyama I, Banerjee A, et al: High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol. 290:C917–C924. 2006. View Article : Google Scholar | |
|
Kim J, Sohn E, Kim CS, Jo K and Kim JS: The role of high-mobility group box-1 protein in the development of diabetic nephropathy. Am J Nephrol. 33:524–529. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Jin J, Gong J, Zhao L, Zhang H, He Q and Jiang X: Inhibition of high mobility group box 1 (HMGB1) attenuates podocyte apoptosis and epithelial-mesenchymal transition by regulating autophagy flux. J Diabetes. 11:826–836. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Lin M, Yiu WH, Wu HJ, Chan LY, Leung JC, Au WS, Chan KW, Lai KN and Tang SC: Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy. J Am Soc Nephrol. 23:86–102. 2012. View Article : Google Scholar | |
|
Zhang H, Zhang R, Chen J, Shi M, Li W and Zhang X: High mobility group box1 inhibitor glycyrrhizic acid attenuates kidney injury in streptozotocin-induced diabetic rats. Kidney Blood Press Res. 42:894–904. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kang R, Livesey KM, Zeh HJ III, Lotze MT and Tang D: HMGB1 as an autophagy sensor in oxidative stress. Autophagy. 7:904–906. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Ling H, Chen H, Wei M, Meng X, Yu Y and Xie K: The effect of autophagy on inflammation cytokines in renal ischemia/reperfusion injury. Inflammation. 39:347–356. 2016. View Article : Google Scholar | |
|
Zhao ZB, Marschner JA, Iwakura T, Li C, Motrapu M, Kuang M, Popper B, Linkermann A, Klocke J, Enghard P, et al: Tubular epithelial cell HMGB1 promotes AKI-CKD transition by sensitizing cycling tubular cells to oxidative stress: A rationale for targeting HMGB1 during AKI recovery. J Am Soc Nephrol. 34:394–411. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Tesch G, Sourris KC, Summers SA, McCarthy D, Ward MS, Borg DJ, Gallo LA, Fotheringham AK, Pettit AR, Yap FY, et al: Deletion of bone-marrow-derived receptor for AGEs (RAGE) improves renal function in an experimental mouse model of diabetes. Diabetologia. 57:1977–1985. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Y, Lu T, Zhang C, Xu J, Xue Z, Busuttil RW, Xu N, Xia Q, Kupiec-Weglinski JW and Ji H: Activation of YAP attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury. J Hepatol. 71:719–730. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Yang K, Fan M, Wang X, Xu J, Wang Y, Tu F, Gill PS, Ha T, Liu L, Williams DL and Li C: Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis. Cell Death Differ. 29:133–146. 2022. View Article : Google Scholar : | |
|
Du S, Zhang X, Jia Y, Peng P, Kong Q, Jiang S, Li Y, Li C, Ding Z and Liu L: Hepatocyte HSPA12A inhibits macrophage chemotaxis and activation to attenuate liver ischemia/reperfusion injury via suppressing glycolysis-mediated HMGB1 lactylation and secretion of hepatocytes. Theranostics. 13:3856–3871. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Wu K, Zha H, Wu T, Liu H, Peng R, Lin Z, Lv D, Liao X, Sun Y and Zhang Z: Cytosolic Hmgb1 accumulation in mesangial cells aggravates diabetic kidney disease progression via NFκB signaling pathway. Cell Mol Life Sci. 81:4082024. View Article : Google Scholar | |
|
Zhu L, Zheng Q, Liu X, Ding H, Ma M, Bao J, Cai Y and Cao C: HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury. Front Immunol. 15:14755432024. View Article : Google Scholar | |
|
Lee JS, See RH, Galvin KM, Wang J and Shi Y: Functional interactions between YY1 and adenovirus E1A. Nucleic Acids Res. 23:925–931. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Shi Y, Seto E, Chang LS and Shenk T: Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 67:377–388. 1991. View Article : Google Scholar : PubMed/NCBI | |
|
Yang T, Shu F, Yang H, Heng C, Zhou Y, Chen Y, Qian X, Du L, Zhu X, Lu Q and Yin X: YY1: A novel therapeutic target for diabetic nephropathy orchestrated renal fibrosis. Metabolism. 96:33–45. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Jha JC, Banal C, Okabe J, Gray SP, Hettige T, Chow BSM, Thallas-Bonke V, De Vos L, Holterman CE, Coughlan MT, et al: NADPH oxidase Nox5 accelerates renal injury in diabetic nephropathy. Diabetes. 66:2691–2703. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Gordon S, Akopyan G, Garban H and Bonavida B: Transcription factor YY1: Structure, function, and therapeutic implications in cancer biology. Oncogene. 25:1125–1142. 2006. View Article : Google Scholar | |
|
Deng Z, Wan M, Cao P, Rao A, Cramer SD and Sui G: Yin Yang 1 regulates the transcriptional activity of androgen receptor. Oncogene. 28:3746–3757. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Gao P, Li L, Yang L, Gui D, Zhang J, Han J, Wang J, Wang N, Lu J, Chen S, et al: Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFbeta1. Sci Transl Med. 11:eaaw20502019. View Article : Google Scholar | |
|
Wei SY, Shih YT, Wu HY, Wang WL, Lee PL, Lee CI, Lin CY, Chen YJ, Chien S and Chiu JJ: Endothelial Yin Yang 1 phosphorylation at S118 induces atherosclerosis under flow. Circ Res. 129:1158–1174. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Du L, Qian X, Li Y, Li XZ, He LL, Xu L, Liu YQ, Li CC, Ma P, Shu FL, et al: Sirt1 inhibits renal tubular cell epithelial-mesenchymal transition through YY1 deacetylation in diabetic nephropathy. Acta Pharmacol Sin. 42:242–251. 2021. View Article : Google Scholar | |
|
Huang J, Wang X, Li N, Fan W, Li X, Zhou Q, Liu J, Li W, Zhang Z, Liu X, et al: YY1 lactylation aggravates autoimmune uveitis by enhancing microglial functions via inflammatory genes. Adv Sci (Weinh). 11:e23080312024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Fan W, Li N, Ma Y, Yao M, Wang G, He S, Li W, Tan J, Lu Q and Hou S: YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. Genome Biol. 24:872023. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshino J, Monkawa T, Tsuji M, Inukai M, Itoh H and Hayashi M: Snail1 is involved in the renal epithelial-mesenchymal transition. Biochem Biophys Res Commun. 362:63–68. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Katoh M and Katoh M: Comparative genomics on SNAI1, SNAI2, and SNAI3 orthologs. Oncol Rep. 14:1083–1086. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Kaufhold S and Bonavida B: Central role of Snail1 in the regulation of EMT and resistance in cancer: A target for therapeutic intervention. J Exp Clin Cancer Res. 33:622014. View Article : Google Scholar : PubMed/NCBI | |
|
Barrallo-Gimeno A and Nieto MA: The Snail genes as inducers of cell movement and survival: Implications in development and cancer. Development. 132:3151–3161. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Grande MT, Sanchez-Laorden B, Lopez-Blau C, De Frutos CA, Boutet A, Arévalo M, Rowe RG, Weiss SJ, López-Novoa JM and Nieto MA: Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med. 21:989–997. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Li SS, Sun Q, Hua MR, Suo P, Chen JR, Yu XY and Zhao YY: Targeting the Wnt/β-catenin signaling pathway as a potential therapeutic strategy in renal tubulointerstitial fibrosis. Front Pharmacol. 12:7198802021. View Article : Google Scholar | |
|
Zhao Y, Yin Z, Li H, Fan J, Yang S, Chen C and Wang DW: MiR-30c protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition in db/db mice. Aging Cell. 16:387–400. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sala L, Franco-Valls H, Stanisavljevic J, Curto J, Vergés J, Peña R, Duch P, Alcaraz J, García de Herreros A and Baulida J: Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. Int J Cancer. 145:3064–3077. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X, He X, Wei W and Huang K: USP22 aggravated diabetic renal tubulointerstitial fibrosis progression through deubiquitinating and stabilizing Snail1. Eur J Pharmacol. 947:1756712023. View Article : Google Scholar : PubMed/NCBI | |
|
Fan M, Yang K, Wang X, Chen L, Gill PS, Ha T, Liu L, Lewis NH, Williams DL and Li C: Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Sci Adv. 9:eadc94652023. View Article : Google Scholar : PubMed/NCBI | |
|
Mao RW, He SP, Lan JG and Zhu WZ: Honokiol ameliorates cisplatin-induced acute kidney injury via inhibition of mitochondrial fission. Br J Pharmacol. 179:3886–3904. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Kleele T, Rey T, Winter J, Zaganelli S, Mahecic D, Perreten Lambert H, Ruberto FP, Nemir M, Wai T, Pedrazzini T and Manley S: Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature. 593:435–439. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Haileselassie B, Mukherjee R, Joshi AU, Napier BA, Massis LM, Ostberg NP, Queliconi BB, Monack D, Bernstein D and Mochly-Rosen D: Drp1/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy. J Mol Cell Cardiol. 130:160–169. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhan M, Usman IM, Sun L and Kanwar YS: Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease. J Am Soc Nephrol. 26:1304–1321. 2015. View Article : Google Scholar | |
|
Huang Q, Chen H, Yin K, Shen Y, Lin K, Guo X, Zhang X, Wang N, Xin W, Xu Y and Gui D: Formononetin attenuates renal tubular injury and mitochondrial damage in diabetic nephropathy partly via regulating Sirt1/PGC-1α pathway. Front Pharmacol. 13:9012342022. View Article : Google Scholar | |
|
Su J, Gao C, Xie L, Fan Y, Shen Y, Huang Q, Wang N, Xu Y, Yang N and Gui D: Astragaloside II ameliorated podocyte injury and mitochondrial dysfunction in streptozotocin-induced diabetic rats. Front Pharmacol. 12:6384222021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Zhu H, Li R, Mui D, Toan S, Chang X and Zhou H: DNA-PKcs interacts with and phosphorylates Fis1 to induce mitochondrial fragmentation in tubular cells during acute kidney injury. Sci Signal. 15:eabh11212022. View Article : Google Scholar : PubMed/NCBI | |
|
Bragoszewski P, Turek M and Chacinska A: Control of mitochondrial biogenesis and function by the ubiquitin-proteasome system. Open Biol. 7:1700072017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang L, Zhang T, Wang L, Cai Y, Zhong X, He X, Hu L, Tian S, Wu M, Hui L, et al: Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission. EMBO J. 36:1330–1347. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
An S, Yao Y, Hu H, Wu J, Li J, Li L, Wu J, Sun M, Deng Z, Zhang Y, et al: PDHA1 hyperacetylation-mediated lactate over-production promotes sepsis-induced acute kidney injury via Fis1 lactylation. Cell Death Dis. 14:4572023. View Article : Google Scholar | |
|
Roberts RE and Hallett MB: Neutrophil cell shape change: Mechanism and signalling during cell spreading and phagocytosis. Int J Mol Sci. 20:13832019. View Article : Google Scholar : PubMed/NCBI | |
|
Wehbi VL and Tasken K: Molecular mechanisms for cAMP-mediated immunoregulation in T cells-role of anchored protein kinase A signaling units. Front Immunol. 7:2222016. View Article : Google Scholar | |
|
Garcia-Ortiz A and Serrador JM: ERM proteins at the crossroad of leukocyte polarization, migration and intercellular Adhesion. Int J Mol Sci. 21:15022020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Li G, Guo Y, Song Y, Chen L, Ruan Q, Wang Y, Sun L, Hu Y, Zhou J, et al: Regulation of ezrin tension by S-nitrosylation mediates non-small cell lung cancer invasion and metastasis. Theranostics. 9:2555–2571. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
McRobert EA and Bach LA: Ezrin contributes to impaired podocyte migration and adhesion caused by advanced glycation end products. Nephrology (Carlton). 21:13–20. 2016. View Article : Google Scholar | |
|
Qiao J, Tan Y, Liu H, Yang B, Zhang Q, Liu Q, Sun W, Li Z, Wang Q, Feng W, et al: Histone H3K18 and ezrin lactylation promote renal dysfunction in sepsis-associated acute kidney injury. Adv Sci (Weinh). 11:e23072162024. View Article : Google Scholar : PubMed/NCBI | |
|
Catrina SB and Zheng X: Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia. 64:709–716. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yamazaki T, Mimura I, Tanaka T and Nangaku M: Treatment of diabetic kidney disease: Current and future. Diabetes Metab J. 45:11–26. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Feng X, Wang S, Sun Z, Dong H, Yu H, Huang M and Gao X: Ferroptosis enhanced diabetic renal tubular injury via HIF-1α/HO-1 pathway in db/db mice. Front Endocrinol (Lausanne). 12:6263902021. View Article : Google Scholar | |
|
Mei S, Li L, Zhou X, Xue C, Livingston MJ, Wei Q, Dai B, Mao Z, Mei C and Dong Z: Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1. FASEB J. 36:e224772022. View Article : Google Scholar : PubMed/NCBI | |
|
Dou L and Jourde-Chiche N: Endothelial toxicity of high glucose and its by-Products in diabetic kidney disease. Toxins (Basel). 11:5782019. View Article : Google Scholar : PubMed/NCBI | |
|
Fu ZJ, Wang ZY, Xu L, Chen XH, Li XX, Liao WT, Ma HK, Jiang MD, Xu TT, Xu J, et al: HIF-1alpha-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury. Redox Biol. 36:1016712020. View Article : Google Scholar | |
|
Sulkshane P, Ram J, Thakur A, Reis N, Kleifeld O and Glickman MH: Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia. Redox Biol. 45:1020472021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu C, Yang M, Li L, Luo S, Yang J, Li C, Liu H and Sun L: A Glimpse of inflammation and Anti-inflammation therapy in diabetic kidney disease. Front Physiol. 13:9095692022. View Article : Google Scholar : PubMed/NCBI | |
|
Luo Y, Yang Z, Yu Y and Zhang P: HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in prostate cancer. Int J Biol Macromol. 222:2225–2243. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Yi W, Clark PM, Mason DE, Keenan MC, Hill C, Goddard WA III, Peters EC, Driggers EM and Hsieh-Wilson LC: Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science. 337:975–980. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Fernandes PM, Kinkead J, McNae I, Michels PAM and Walkinshaw MD: Biochemical and transcript level differences between the three human phosphofructokinases show optimisation of each isoform for specific metabolic niches. Biochem J. 477:4425–4441. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lang L, Chemmalakuzhy R, Shay C and Teng Y: PFKP signaling at a glance: An emerging mediator of cancer cell metabolism. Adv Exp Med Biol. 1134:243–258. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Meira DD, Marinho-Carvalho MM, Teixeira CA, Veiga VF, Da Poian AT, Holandino C, de Freitas MS and Sola-Penna M: Clotrimazole decreases human breast cancer cells viability through alterations in cytoskeleton-associated glycolytic enzymes. Mol Genet Metab. 84:354–362. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Liang W, Luo Q, Hu H, Yang K, Hu J, Chen Z, Zhu J, Feng J, Zhu Z, et al: PFKP activation ameliorates foot process fusion in podocytes in diabetic kidney disease. Front Endocrinol (Lausanne). 12:7970252021. View Article : Google Scholar | |
|
Cheng Z, Huang H, Li M and Chen Y: Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells. iScience. 27:1086452024. View Article : Google Scholar | |
|
Pritchett J, Athwal V, Roberts N, Hanley NA and Hanley KP: Understanding the role of SOX9 in acquired diseases: Lessons from development. Trends Mol Med. 17:166–174. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Symon A and Harley V: SOX9: A genomic view of tissue specific expression and action. Int J Biochem Cell Biol. 87:18–22. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lefebvre V and Dvir-Ginzberg M: SOX9 and the many facets of its regulation in the chondrocyte lineage. Connect Tissue Res. 58:2–14. 2017. View Article : Google Scholar | |
|
Grimm D, Bauer J, Wise P, Krüger M, Simonsen U, Wehland M, Infanger M and Corydon TJ: The role of SOX family members in solid tumours and metastasis. Semin Cancer Biol. 67:122–153. 2020. View Article : Google Scholar | |
|
Kishi S, Abe H, Akiyama H, Tominaga T, Murakami T, Mima A, Nagai K, Kishi F, Matsuura M, Matsubara T, et al: SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy. J Biol Chem. 286:32162–32169. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Cai H, Deng J, Tu X, Sun Y, Huang Z, Ding Z, Dong L, Chen J, Zang Y and Zhang J: TGF-β-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis. Biochim Biophys Acta Mol Basis Dis. 1864:520–532. 2018. View Article : Google Scholar | |
|
Yan F, Teng Y, Li X, Zhong Y, Li C, Yan F and He X: Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9. Cancer Biol Ther. 25:23041612024. View Article : Google Scholar : PubMed/NCBI | |
|
Baubec T, Ivanek R, Lienert F and Schubeler D: Methylation-dependent and -independent genomic targeting principles of the MBD protein family. Cell. 153:480–492. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Clouaire T and Stancheva I: Methyl-CpG binding proteins: Specialized transcriptional repressors or structural components of chromatin? Cell Mol Life Sci. 65:1509–1522. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng TL, Wang Z, Liao Q, Zhu Y, Zhou WH, Xu W and Qiu Z: MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Dev Cell. 28:547–560. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Partscht P, Simon A, Chen NP, Erhardt S and Schiebel E: The HIPK2/CDC14B-MeCP2 axis enhances the spindle assembly checkpoint block by promoting cyclin B translation. Sci Adv. 9:eadd69822023. View Article : Google Scholar : PubMed/NCBI | |
|
Oh HJ, Kato M, Deshpande S, Zhang E, Das S, Lanting L, Wang M and Natarajan R: Inhibition of the processing of miR-25 by HIPK2-Phosphorylated-MeCP2 induces NOX4 in early diabetic nephropathy. Sci Rep. 6:387892016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Chen L, Zhang M, Li X, Yang X, Huang T, Ban Y, Li Y, Li Q, Zheng Y, et al: Exercise-induced endothelial Mecp2 lactylation suppresses atherosclerosis via the Ereg/MAPK signalling pathway. Atherosclerosis. 375:45–58. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Ingham RJ, Gish G and Pawson T: The Nedd4 family of E3 ubiquitin ligases: Functional diversity within a common modular architecture. Oncogene. 23:1972–1984. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, Wang J, Erdjument-Bromage H, Tempst P, Cordon-Cardo C, et al: NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 128:129–139. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Fujio Y, Nguyen T, Wencker D, Kitsis RN and Walsh K: Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 101:660–667. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Murdaca J, Treins C, Monthouel-Kartmann MN, Pontier-Bres R, Kumar S, Van Obberghen E and Giorgetti-Peraldi S: Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation. J Biol Chem. 279:26754–26761. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Han F, Wu S, Dong Y, Liu Y, Sun B and Chen L: Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by downregulating CaMKKβ in diabetic kidney disease. J Transl Med. 22:4652024. View Article : Google Scholar | |
|
Henshall TL, Manning JA, Alfassy OS, Goel P, Boase NA, Kawabe H and Kumar S: Deletion of Nedd4-2 results in progressive kidney disease in mice. Cell Death Differ. 24:2150–2160. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Al-Qusairi L, Basquin D, Roy A, Rajaram RD, Maillard MP, Subramanya AR and Staub O: Renal tubular Ubiquitin-Protein ligase NEDD4-2 is required for renal adaptation during long-term potassium depletion. J Am Soc Nephrol. 28:2431–2442. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wu P, Su XT, Gao ZX, Zhang DD, Duan XP, Xiao Y, Staub O, Wang WH and Lin DH: Renal tubule Nedd4-2 deficiency stimulates Kir4.1/Kir5.1 and Thiazide-sensitive NaCl cotransporter in distal convoluted tubule. J Am Soc Nephrol. 31:1226–1242. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Li Q, Zhang F, Wang H, Tong Y, Fu Y, Wu K, Li J, Wang C, Wang Z, Jia Y, et al: NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis. Int J Biol Sci. 20:1413–1435. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Aksan I and Goding CR: Targeting the microphthalmia basic helix-loop-helix-leucine zipper transcription factor to a subset of E-box elements in vitro and in vivo. Mol Cell Biol. 18:6930–6938. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, et al: TFEB links autophagy to lysosomal biogenesis. Science. 332:1429–1433. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Song JX, Sun YR, Peluso I, Zeng Y, Yu X, Lu JH, Xu Z, Wang MZ, Liu LF, Huang YY, et al: A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition. Autophagy. 12:1372–1389. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kim SH, Kim G, Han DH, Lee M, Kim I, Kim B, Kim KH, Song YM, Yoo JE, Wang HJ, et al: Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition. Autophagy. 13:1767–1781. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Erdin S, Huynh T, Ferron M, Karsenty G, Vellard MC, et al: A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31:1095–1108. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan Y, Li L, Zhu L, Liu F, Tang X, Liao G, Liu J, Cheng J, Chen Y and Lu Y: Mesenchymal stem cells elicit macrophages into M2 phenotype via improving transcription factor EB-mediated autophagy to alleviate diabetic nephropathy. Stem Cells. 38:639–652. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Rask-Madsen C and King GL: Diabetes: Podocytes lose their footing. Nature. 468:42–44. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X, Chen Y, Tan X, Zhang L, Zhang H, Li Z, Liu S, Li R, Lin T, Liao R, et al: Advanced glycation end-products suppress autophagic flux in podocytes by activating mammalian target of rapamycin and inhibiting nuclear translocation of transcription factor EB. J Pathol. 245:235–248. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Jacinto E: TFEBulous control of traffic by mTOR. EMBO J. 30:3215–3216. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Li T, Yin L, Kang X, Xue W, Wang N, Zhang J, Yuan P, Lin L and Li Y: TFEB acetylation promotes lysosome biogenesis and ameliorates Alzheimer's disease-relevant phenotypes in mice. J Biol Chem. 298:1026492022. View Article : Google Scholar : PubMed/NCBI | |
|
Martina JA and Puertollano R: Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress. J Biol Chem. 293:12525–12534. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Settembre C, De Cegli R, Mansueto G, Saha PK, Vetrini F, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch TJ, et al: TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol. 15:647–658. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Sha Y, Rao L, Settembre C, Ballabio A and Eissa NT: STUB1 regulates TFEB-induced autophagy-lysosome pathway. EMBO J. 36:2544–2552. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Y, Luo G, Peng K, Song Y, Wang Y, Zhang H, Li J, Qiu X, Pu M, Liu X, et al: Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity. J Cell Biol. 223:e2023080992024. View Article : Google Scholar : PubMed/NCBI | |
|
Qu D, Jiang M, Huang D, Zhang H, Feng L, Chen Y, Zhu X, Wang S and Han J: Synergistic effects of the enhancements to mitochondrial ROS, p53 activation and apoptosis generated by aspartame and potassium sorbate in HepG2 cells. Molecules. 24:4572019. View Article : Google Scholar : PubMed/NCBI | |
|
Kruiswijk F, Labuschagne CF and Vousden KH: p53 in survival, death and metabolic health: A lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 16:393–405. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Saldana-Meyer R and Recillas-Targa F: Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics. 6:1068–1077. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Mulay SR, Thomasova D, Ryu M and Anders HJ: MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice. Kidney Int. 81:1199–1211. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Peng J, Li X, Zhang D, Chen JK, Su Y, Smith SB and Dong Z: Hyperglycemia, p53, and mitochondrial pathway of apoptosis are involved in the susceptibility of diabetic models to ischemic acute kidney injury. Kidney Int. 87:137–150. 2015. View Article : Google Scholar : | |
|
Yang R, Xu X, Li H, Chen J, Xiang X, Dong Z and Zhang D: p53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO. Sci Rep. 7:434092017. View Article : Google Scholar : PubMed/NCBI | |
|
Brezniceanu ML, Liu F, Wei CC, Chénier I, Godin N, Zhang SL, Filep JG, Ingelfinger JR and Chan JS: Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells. Diabetes. 57:451–459. 2008. View Article : Google Scholar | |
|
Brezniceanu ML, Liu F, Wei CC, Tran S, Sachetelli S, Zhang SL, Guo DF, Filep JG, Ingelfinger JR and Chan JS: Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int. 71:912–923. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Qi R, Wang J, Jiang Y, Qiu Y, Xu M, Rong R and Zhu T: Snai1-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation. Cell Death Dis. 12:442021. View Article : Google Scholar | |
|
Sutton TA, Hato T, Mai E, Yoshimoto M, Kuehl S, Anderson M, Mang H, Plotkin Z, Chan RJ and Dagher PC: p53 is renoprotective after ischemic kidney injury by reducing inflammation. J Am Soc Nephrol. 24:113–124. 2013. View Article : Google Scholar : | |
|
Zong Z, Xie F, Wang S, Wu X, Zhang Z, Yang B and Zhou F: Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell. 187:2375–2392.e33. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Russo GL, Russo M and Ungaro P: AMP-activated protein kinase: A target for old drugs against diabetes and cancer. Biochem Pharmacol. 86:339–350. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Momcilovic M, Hong SP and Carlson M: Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J Biol Chem. 281:25336–25343. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Rogacka D, Piwkowska A, Audzeyenka I, Angielski S and Jankowski M: Involvement of the AMPK-PTEN pathway in insulin resistance induced by high glucose in cultured rat podocytes. Int J Biochem Cell Biol. 51:120–130. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jørgensen SB, Viollet B, Andreelli F, Frøsig C, Birk JB, Schjerling P, Vaulont S, Richter EA and Wojtaszewski JF: Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. J Biol Chem. 279:1070–1079. 2004. View Article : Google Scholar | |
|
Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P and Auwerx J: AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 458:1056–1060. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Godel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S, Debreczeni-Mór A, Lindenmeyer MT, Rastaldi MP and Hartleben G: Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Invest. 121:2197–2209. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Guo H, Wang Y, Zhang X, Zang Y, Zhang Y, Wang L, Wang H, Wang Y, Cao A and Peng W: Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy. Sci Rep. 7:68522017. View Article : Google Scholar | |
|
Zhang Y, Huang Z, Han W, Wu J, Li S, Qin T, Zhang C, Shi M, Han S, Gao B, et al: Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration. Commun Biol. 7:3252024. View Article : Google Scholar | |
|
Hou X, Hong Z, Zeng H, Zhang C, Zhang P, Ma D and Han Z: Lactylation in cancer biology: Unlocking new avenues for research and therapy. Cancer Commun (Lond). 45:1367–1406. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Z, Peng Y, Chen W, Xia F, Song T and Ke Q: Lactylation-driven transcriptional activation of FBXO33 promotes gallbladder cancer metastasis by regulating p53 polyubiquitination. Cell Death Dis. 16:1442025. View Article : Google Scholar : PubMed/NCBI | |
|
Feng L, Feng YY, Ren Q, Fu P and Ma L: Mesangial cells in diabetic kidney disease: From mechanisms to therapeutic implications. Int J Biol Sci. 21:4762–4781. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang S, Luo M, Lu Z and Shi Q: Lactate and lactylation in sepsis-associated acute kidney injury: Clinical evidence from the MIMIC-IV database and mechanistic insights. Front Med (Lausanne). 12:17081452025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang D, Liang C, Wu C, Hawanga M, Wan S, Xu L, Zhang X, Liu Y, Hu F, Wang M, et al: Nonhistone lactylation: A hub for tumour metabolic reprogramming and epigenetic regulation. J Transl Med. 23:9012025. View Article : Google Scholar : PubMed/NCBI | |
|
Kung CP and Murphy ME: The role of the p53 tumor suppressor in metabolism and diabetes. J Endocrinol. 231:R61–R75. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Sun T, Liu B, Li Y, Wu J, Cao Y, Yang S, Tan H, Cai L, Zhang S, Qi X, et al: Oxamate enhances the efficacy of CAR-T therapy against glioblastoma via suppressing ectonucleotidases and CCR8 lactylation. J Exp Clin Cancer Res. 42:2532023. View Article : Google Scholar : PubMed/NCBI | |
|
Marlier JF, Cleland WW and Zeczycki TN: Oxamate is an alternative substrate for pyruvate carboxylase from Rhizobium etli. Biochemistry. 52:2888–2894. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Altinoz MA and Ozpinar A: Oxamate targeting aggressive cancers with special emphasis to brain tumors. Biomed Pharmacother. 147:1126862022. View Article : Google Scholar : PubMed/NCBI | |
|
Ye W, Zheng Y, Zhang S, Yan L, Cheng H and Wu M: Oxamate improves glycemic control and insulin sensitivity via inhibition of tissue lactate production in db/db Mice. PLoS One. 11:e01503032016. View Article : Google Scholar : PubMed/NCBI | |
|
Friberg A, Rehwinkel H, Nguyen D, Pütter V, Quanz M, Weiske J, Eberspächer U, Heisler I and Langer G: Structural evidence for isoform-selective allosteric inhibition of lactate dehydrogenase A. ACS Omega. 5:13034–13041. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hollenberg AM, Smith CO, Shum LC, Awad H and Eliseev RA: Lactate dehydrogenase inhibition with oxamate exerts bone anabolic effect. J Bone Miner Res. 35:2432–2443. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Qiao T, Xiong Y, Feng Y, Guo W, Zhou Y, Zhao J, Jiang T, Shi C and Han Y: Inhibition of LDH-A by oxamate enhances the efficacy of Anti-PD-1 treatment in an NSCLC humanized mouse model. Front Oncol. 11:6323642021. View Article : Google Scholar : PubMed/NCBI | |
|
Shibata S, Sogabe S, Miwa M, Fujimoto T, Takakura N, Naotsuka A, Kitamura S, Kawamoto T and Soga T: Identification of the first highly selective inhibitor of human lactate dehydrogenase B. Sci Rep. 11:213532021. View Article : Google Scholar : PubMed/NCBI | |
|
Rai G, Brimacombe KR, Mott BT, Urban DJ, Hu X, Yang SM, Lee TD, Cheff DM, Kouznetsova J, Benavides GA, et al: Discovery and optimization of potent, Cell-active pyrazole-based inhibitors of lactate dehydrogenase (LDH). J Med Chem. 60:9184–9204. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Han JH, Lee EJ, Park W, Ha KT and Chung HS: Natural compounds as lactate dehydrogenase inhibitors: Potential therapeutics for lactate dehydrogenase inhibitors-related diseases. Front Pharmacol. 14:12750002023. View Article : Google Scholar : PubMed/NCBI | |
|
El Hassouni B, Franczak M, Capula M, Vonk CM, Gomez VM, Smolenski RT, Granchi C, Peters GJ, Minutolo F and Giovannetti E: Lactate dehydrogenase A inhibition by small molecular entities: Steps in the right direction. Oncoscience. 7:76–80. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hwang D, Kim T, Kyun S, Jang I, Park HY, Kim SW, Han JS, So JM, Lee CH, Park J, et al: Oxamate suppresses whole-body energy metabolism at rest and during exercise in mice by inhibiting fat oxidation and altering lactate dynamics. Phys Act Nutr. 29:26–34. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Zhai X, Yang Y, Wan J, Zhu R and Wu Y: Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep. 30:2983–2991. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Ouyang J, Wang H and Huang J: The role of lactate in cardiovascular diseases. Cell Commun Signal. 21:3172023. View Article : Google Scholar : PubMed/NCBI | |
|
Cui D and Morris ME: The drug of abuse gamma-hydroxybutyrate is a substrate for sodium-coupled monocarboxylate transporter (SMCT) 1 (SLC5A8): Characterization of SMCT-mediated uptake and inhibition. Drug Metab Dispos. 37:1404–1410. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Emoto A, Ushigome F, Koyabu N, Kajiya H, Okabe K, Satoh S, Tsukimori K, Nakano H, Ohtani H and Sawada Yl: H(+)-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo. Am J Physiol Cell Physiol. 282:C1064–C1075. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Richard AN, Natalie B, Helen B, Sikka A, Thomas H, Phillips N, Nakjang S, Miwa S, Crossland R, Rand V, et al: Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma. Haematologica. 102:1247–1257. 2017. View Article : Google Scholar | |
|
Bola BM, Chadwick AL, Michopoulos F, Blount KG, Telfer BA, Williams KJ, Smith PD, Critchlow SE and Stratford IJ: Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol Cancer Ther. 13:2805–2816. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Beloueche-Babari M, Wantuch S, Casals Galobart T, Koniordou M, Parkes HG, Arunan V, Chung YL, Eykyn TR, Smith PD and Leach MO: MCT1 Inhibitor AZD3965 increases mitochondrial metabolism, facilitating combination therapy and noninvasive magnetic resonance spectroscopy. Cancer Res. 77:5913–5924. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Xu Z and Wang X, Cheng H, Li J, Zhang X and Wang X: The role of MCT1 in tumor progression and targeted therapy: A comprehensive review. Front Immunol. 16:16104662025. View Article : Google Scholar : PubMed/NCBI | |
|
Halford SER, Jones P, Wedge S, Hirschberg S, Katugampola S, Veal G, Payne G and Plummer ER: A first-in-human first-in-class (FIC) trial of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in patients with advanced solid tumours. J Clin Oncol. 35:2516. 2017. View Article : Google Scholar | |
|
Halford S, Veal GJ, Wedge SR, Payne GS, Bacon CM, Sloan P, Dragoni I, Heinzmann K, Potter S, Salisbury BM, et al: A Phase I Dose-escalation Study of AZD3965, an oral monocarboxylate transporter 1 inhibitor, in patients with advanced cancer. Clin Cancer Res. 29:1429–1439. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Huang T, Feng Q, Wang Z, Li W, Sun Z, Wilhelm J, Huang G, Vo T, Sumer BD and Gao J: Tumor-Targeted inhibition of monocarboxylate transporter 1 improves T-cell immunotherapy of solid tumors. Adv Healthc Mater. 10:20005492021. View Article : Google Scholar | |
|
Wu G, Pan Y, Chen M, Liu Z, Li C, Sheng Y, Li H, Shen M and Liu H: Lactylation drives hCG-triggered luteinization in hypoxic granulosa cells. Int J Biol Macromol. 280:1355802024. View Article : Google Scholar : PubMed/NCBI | |
|
Leng S, Huang W, Chen Y, Yang Y, Feng D, Liu W, Gao T, Ren Y, Huo M, Zhang J, et al: SIRT1 coordinates with the CRL4B complex to regulate pancreatic cancer stem cells to promote tumorigenesis. Cell Death Differ. 28:3329–3343. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Peng J, Li J, Huang J, Xu P, Huang H, Liu Y, Yu L, Yang Y, Zhou B, Jiang H, et al: p300/CBP inhibitor A-485 alleviates acute liver injury by regulating macrophage activation and polarization. Theranostics. 9:8344–8361. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Jaschke NP, Breining D, Hofmann M, Pählig S, Baschant U, Oertel R, Traikov S, Grinenko T, Saettini F, Biondi A, et al: Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response. Immunity. 57:364–378.e9. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Ji C, Xu W, Ding H, Chen Z, Shi C, Han J, Yu L, Qiao N, Zhang Y, Cao X, et al: The p300 inhibitor A-485 exerts antitumor activity in growth hormone pituitary adenoma. J Clin Endocrinol Metab. 107:e2291–e2300. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Ansari MSZ, Stagni V, Iuzzolino A, Rotili D, Mai A, Del Bufalo D, Lavia P, Degrassi F and Trisciuoglio D: Pharmacological targeting of CBP/p300 drives a redox/autophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells. Cancer Gene Therapy. 30:124–136. 2023. View Article : Google Scholar : | |
|
Dai SK, Liu PP, Li X, Jiao LF, Teng ZQ and Liu CM: Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development. Development. 149:dev2000492022. View Article : Google Scholar : PubMed/NCBI | |
|
Bursch KL, Goetz CJ and Smith BC: Current trends in sirtuin activator and inhibitor development. Molecules. 29:11852024. View Article : Google Scholar : PubMed/NCBI | |
|
Yu S, Li Y, Lu X, Han Z, Li C, Yuan X and Guo D: The regulatory role of miRNA and lncRNA on autophagy in diabetic nephropathy. Cell Signal. 118:1111442024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y and Zhang X: Virus-induced histone lactylation promotes virus infection in crustacean. Adv Sci (Weinh). 11:e24010172024. View Article : Google Scholar : PubMed/NCBI | |
|
Liu L, Chen Y, Li X, Wang J and Yang L: Therapeutic potential: The role of mesenchymal stem cells from diverse sources and their derived exosomes in diabetic nephropathy. Biomed Pharmacother. 175:1166722024. View Article : Google Scholar : PubMed/NCBI | |
|
van Son J, Oussaada SM, Şekercan A, Beudel M, Dongelmans DA, van Assen S, Eland IA, Moeniralam HS, Dormans TPJ, van Kalkeren CAJ, et al: Overweight and obesity are associated with acute kidney injury and acute respiratory distress syndrome, but not with increased mortality in hospitalized COVID-19 patients: A retrospective cohort study. Front Endocrinol (Lausanne). 12:7477322021. View Article : Google Scholar : | |
|
Schiller M, Solger K, Leipold S, Kerl HU and Kick W: Diabetes-associated nephropathy and obesity influence COVID-19 outcome in type 2 diabetes patients. J Community Hosp Intern Med Perspect. 11:590–596. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Gao M, Piernas C, Astbury NM, Hippisley-Cox J, O'Rahilly S, Aveyard P and Jebb SA: Associations between body-mass index and COVID-19 severity in 6•9 million people in England: A prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 9:350–359. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Sörling A, Nordberg P, Hofmann R, Häbel H and Svensson P: Association between CKD, obesity, cardiometabolic risk factors, and severe COVID-19 outcomes. Kidney Int Rep. 8:775–784. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Martín-Del-Campo F, Ruvalcaba-Contreras N, Velázquez-Vidaurri AL, Cueto-Manzano AM, Rojas-Campos E, Cortés-Sanabria L, Espinel-Bermúdez MC, Hernández-González SO, Nava-Zavala AH, Fuentes-Orozco C, et al: Morbid obesity is associated with mortality and acute kidney injury in hospitalized patients with COVID-19. Clin Nutr ESPEN. 45:200–205. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Al-Sabah S, Al-Haddad M, Al-Youha S, Jamal M and Almazeedi S: COVID-19: Impact of obesity and diabetes on disease severity. Clin Obes. 10:e124142020. View Article : Google Scholar : PubMed/NCBI | |
|
Li LN, Li WW, Xiao LS and Lai WN: Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma. Front Immunol. 15:14333932024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang P, Xie D, Xiao T, Cheng C, Wang D, Sun J, Wu M, Yang Y, Zhang A and Liu Q: H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP. J Hazard Mater. 461:1325822024. View Article : Google Scholar | |
|
Liang H, Xu L and Yang Y: Lactate and lactylation: Novel perspectives on fibrosis pathogenesis and therapeutic directions. J Transl Med. 23:7052025. View Article : Google Scholar : PubMed/NCBI | |
|
Nechipurenko YD, Semyonov DA, Lavrinenko IA, Lagutkin DA, Generalov EA, Zaitceva AY, Matveeva OV and Yegorov YE: The role of acidosis in the pathogenesis of severe forms of COVID-19. Biology (Basel). 10:8522021.PubMed/NCBI | |
|
Wang X, Li Y, Qiang G, Wang K, Dai J, McCann M, Munoz MD, Gil V, Yu Y, Li S, et al: Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice. Nat Commun. 13:73232022. View Article : Google Scholar : PubMed/NCBI | |
|
Gupta GS: The lactate and the lactate dehydrogenase in inflammatory diseases and major risk factors in COVID-19 patients. Inflammation. 45:2091–2123. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Bao C, Ma Q, Ying X, Wang F, Hou Y, Wang D, Zhu L, Huang J and He C: Histone lactylation in macrophage biology and disease: From plasticity regulation to therapeutic implications. eBioMedicine. 111:1055022025. View Article : Google Scholar : | |
|
Li C, Fu C, Zhou W, Li H, Liu Z, Wu G, He T, Shen M and Liu H: Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition. Cell Commun Signal. 23:3642025. View Article : Google Scholar | |
|
Thyrsted J, Storgaard J, Blay-Cadanet J, Heinz A, Thielke AL, Crotta S, de Paoli F, Olagnier D, Wack A, Hiller K, et al: Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium. iScience. 24:1033002021. View Article : Google Scholar : PubMed/NCBI | |
|
Wu J, Li Y, Yang Y, Chen R, Wang H, Xie K, Lan J, Guo M, Zhang Y and Li X: Wogonoside inhibits fibroblast activation and pulmonary fibrosis by dual regulation of Snail1 lactylation and PGC1α/PINK1-mediated mitophagy. Phytomedicine. 147:1572402025. View Article : Google Scholar |