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Review Open Access

TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review)

  • Authors:
    • Jianchun Li
    • Yuanxia Zou
    • Jiraporn Kantapan
    • Hongwei Su
    • Li Wang
    • Nathupakorn Dechsupa
  • View Affiliations / Copyright

    Affiliations: Department of Radiologic Technology, Molecular Imaging and Therapy Research Unit, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand, Department of Urology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 143
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    Published online on: June 18, 2024
       https://doi.org/10.3892/mmr.2024.13267
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Abstract

The TGF‑β/Smad signaling pathway plays a pivotal role in the onset of glomerular and tubulointerstitial fibrosis in chronic kidney disease (CKD). The present review delves into the intricate post‑translational modulation of this pathway and its implications in CKD. Specifically, the impact of the TGF‑β/Smad pathway on various biological processes was investigated, encompassing not only renal tubular epithelial cell apoptosis, inflammation, myofibroblast activation and cellular aging, but also its role in autophagy. Various post‑translational modifications (PTMs), including phosphorylation and ubiquitination, play a crucial role in modulating the intensity and persistence of the TGF‑β/Smad signaling pathway. They also dictate the functionality, stability and interactions of the TGF‑β/Smad components. The present review sheds light on recent findings regarding the impact of PTMs on TGF‑β receptors and Smads within the CKD landscape. In summary, a deeper insight into the post‑translational intricacies of TGF‑β/Smad signaling offers avenues for innovative therapeutic interventions to mitigate CKD progression. Ongoing research in this domain holds the potential to unveil powerful antifibrotic treatments, aiming to preserve renal integrity and function in patients with CKD.
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1 

Webster AC, Nagler EV, Morton RL and Masson P: Chronic kidney disease. Lancet. 389:1238–1252. 2017. View Article : Google Scholar : PubMed/NCBI

2 

GBD Chronic Kidney Disease Collaboration, . Global, regional, and national burden of chronic kidney disease, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 395:709–733. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Chen TK, Knicely DH and Grams ME: Chronic kidney disease diagnosis and management: A review. JAMA. 322:1294–1304. 2019. View Article : Google Scholar : PubMed/NCBI

4 

Liu Y: Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol. 7:684–696. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Meng X, Nikolic-Paterson DJ and Lan HY: TGF-β: The master regulator of fibrosis. Nat Rev Nephrol. 12:325–338. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A and Rodrigues-Diez RR: Targeting the progression of chronic kidney disease. Nat Rev Nephrol. 16:269–288. 2020. View Article : Google Scholar : PubMed/NCBI

7 

Gu YY, Liu XS, Huang XR, Yu XQ and Lan HY: TGF-β in renal fibrosis: Triumphs and challenges. Future Med Chem. 12:853–866. 2020. View Article : Google Scholar : PubMed/NCBI

8 

Wu W, Wang X, Yu X and Lan HY: Smad3 Signatures in Renal Inflammation and Fibrosis. Int J Biol Sci. 18:2795–2806. 2022. View Article : Google Scholar : PubMed/NCBI

9 

Meng XM, Tang PM, Li J and Lan HY: TGF-β/Smad signaling in renal fibrosis. Front Physiol. 6:822015. View Article : Google Scholar : PubMed/NCBI

10 

Yu L, Border WA, Huang Y and Noble NA: TGF-beta isoforms in renal fibrogenesis. Kidney Int. 64:844–856. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Weiss A and Attisano L: The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol. 2:47–63. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Annes JP, Munger JS and Rifkin DB: Making sense of latent TGFbeta activation. J Cell Sci. 116:217–224. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Robertson IB, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K and Rifkin DB: Latent TGF-β-binding proteins. Matrix Biol. 47:44–53. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Macconi D, Remuzzi G and Benigni A: Key fibrogenic mediators: Old players. Renin-angiotensin system. Kidney Int. Suppl (2011):4:58–64. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Loeffler I and Wolf G: Transforming growth factor-β and the progression of renal disease. Nephrol Dial Transplant. 29 (Suppl 1):i37–i45. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Samarakoon R, Overstreet JM and Higgins PJ: TGF-β signaling in tissue fibrosis: Redox controls, target genes and therapeutic opportunities. Cell Signal. 25:264–268. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Samarakoon R, Overstreet JM, Higgins SP and Higgins PJ: TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis. Cell Tissue Res. 347:117–128. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Li J, Yang J, Zhu B, Fan J, Hu Q and Wang L: Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3-mediated ferroptosis and fibrosis. Phytother Res. 36:475–487. 2022. View Article : Google Scholar : PubMed/NCBI

19 

Yang Q, Gao L, Hu XW, Wang JN, Zhang Y, Dong YH, Lan HY and Meng XM: Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by attenuating programmed cell death and inflammation via a NOX4-dependent mechanism. Kidney Dis (Basel). 7:372–390. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Tang PM, Zhou S, Li CJ, Liao J, Xiao J, Wang QM, Lian GY, Li J, Huang XR, To KF, et al: The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring. Kidney Int. 93:173–187. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Liang L, Wang W, Chen J, Wu W, Huang XR, Wei B, Zhong Y, Ma RCW, Yu X and Lan HY: SARS-CoV-2 N protein induces acute kidney injury in diabetic mice via the Smad3-Ripk3/MLKL necroptosis pathway. Signal Transduct Target Ther. 8:1472023. View Article : Google Scholar : PubMed/NCBI

22 

Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA Jr, Wrana JL and Falb D: The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 89:1165–1173. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Zhang Y, Feng XH and Derynck R: Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 394:909–913. 1998. View Article : Google Scholar : PubMed/NCBI

24 

Samarakoon R, Dobberfuhl AD, Cooley C, Overstreet JM, Patel S, Goldschmeding R, Meldrum KK and Higgins PJ: Induction of renal fibrotic genes by TGF-β1 requires EGFR activation, p53 and reactive oxygen species. Cell Signal. 25:2198–2209. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Samarakoon R, Higgins SP, Higgins CE and Higgins PJ: TGF-beta1-induced plasminogen activator inhibitor-1 expression in vascular smooth muscle cells requires pp60(c-src)/EGFR(Y845) and Rho/ROCK signaling. J Mol Cell Cardiol. 44:527–538. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Meng XM, Chung ACK and Lan HY: Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci (Lond). 124:243–254. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Zhang YE: Non-Smad signaling pathways of the TGF-β Family. Cold Spring Harb Perspect Biol. 9:a0221292017. View Article : Google Scholar : PubMed/NCBI

28 

Kim SI and Choi ME: TGF-β-activated kinase-1: New insights into the mechanism of TGF-β signaling and kidney disease. Kidney Res Clin Pract. 31:94–105. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Humphreys BD: Mechanisms of Renal Fibrosis. Annu Rev Physiol. 80:309–326. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Lin SL, Kisseleva T, Brenner DA and Duffield JS: Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol. 173:1617–1627. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Nakamura J, Sato Y, Kitai Y, Wajima S, Yamamoto S, Oguchi A, Yamada R, Kaneko K, Kondo M, Uchino E, et al: Myofibroblasts acquire retinoic acid-producing ability during fibroblast-to-myofibroblast transition following kidney injury. Kidney Int. 95:526–539. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Chen YT, Chang FC, Wu CF, Chou YH, Hsu HL, Chiang WC, Shen J, Chen YM, Wu KD, Tsai TJ, et al: Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. Kidney Int. 80:1170–1181. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Kramann R, Schneider RK, DiRocco DP, Machado F, Fleig S, Bondzie PA, Henderson JM, Ebert BL and Humphreys BD: Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell. 16:51–66. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Li J, Qu X and Bertram JF: Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol. 175:1380–1388. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Meng X, Jin J and Lan HY: Driving role of macrophages in transition from acute kidney injury to chronic kidney disease. Chin Med J (Engl). 135:757–766. 2022. View Article : Google Scholar : PubMed/NCBI

36 

Zeisberg M and Kalluri R: The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med (Berl). 82:175–181. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Kim KK, Sheppard D and Chapman HA: TGF-β1 signaling and tissue fibrosis. Cold Spring Harb Perspect Biol. 10:a0222932018. View Article : Google Scholar : PubMed/NCBI

38 

Meng XM, Huang XR, Chung AC, Qin W, Shao X, Igarashi P, Ju W, Bottinger EP and Lan HY: Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. J Am Soc Nephrol. 21:1477–1487. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Sato M, Muragaki Y, Saika S, Roberts AB and Ooshima A: Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest. 112:1486–1494. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Zarjou A, Yang S, Abraham E, Agarwal A and Liu G: Identification of a microRNA signature in renal fibrosis: Role of miR-21. Am J Physiol Renal Physiol. 301:F793–F801. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Zhong X, Chung AC, Chen HY, Meng XM and Lan HY: Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol. 22:1668–1681. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Wang B, Komers R, Carew R, Winbanks CE, Xu B, Herman-Edelstein M, Koh P, Thomas M, Jandeleit-Dahm K, Gregorevic P, et al: Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 23:252–265. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Meng XM, Wang S, Huang XR, Yang C, Xiao J, Zhang Y, To KF, Nikolic-Paterson DJ and Lan HY: Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis. Cell Death Dis. 7:e24952016. View Article : Google Scholar : PubMed/NCBI

44 

Wang YY, Jiang H, Pan J, Huang XR, Wang YC, Huang HF, To KF, Nikolic-Paterson DJ, Lan HY and Chen JH: Macrophage-to-Myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. J Am Soc Nephrol. 28:2053–2067. 2017. View Article : Google Scholar : PubMed/NCBI

45 

Wei J, Xu Z and Yan X: The role of the macrophage-to-myofibroblast transition in renal fibrosis. Front Immunol. 13:9343772022. View Article : Google Scholar : PubMed/NCBI

46 

Tang PM, Zhang YY, Xiao J, Tang PC, Chung JY, Li J, Xue VW, Huang XR, Chong CC, Ng CF, et al: Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition. Proc Natl Acad Sci USA. 117:20741–20752. 2020. View Article : Google Scholar : PubMed/NCBI

47 

Wang S, Meng XM, Ng YY, Ma FY, Zhou S, Zhang Y, Yang C, Huang XR, Xiao J, Wang YY, et al: TGF-β/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis. Oncotarget. 7:8809–8822. 2016. View Article : Google Scholar : PubMed/NCBI

48 

Chen J, Tang Y, Zhong Y, Wei B, Huang XR, Tang PM, Xu A and Lan HY: P2Y12 inhibitor clopidogrel inhibits renal fibrosis by blocking macrophage-to-myofibroblast transition. Mol Ther. 30:3017–3033. 2022. View Article : Google Scholar : PubMed/NCBI

49 

Xavier S, Vasko R, Matsumoto K, Zullo JA, Chen R, Maizel J, Chander PN and Goligorsky MS: Curtailing endothelial TGF-β signaling is sufficient to reduce endothelial-mesenchymal transition and fibrosis in CKD. J Am Soc Nephrol. 26:817–829. 2015. View Article : Google Scholar : PubMed/NCBI

50 

LeBleu VS, Taduri G, O'Connell J, Teng Y, Cooke VG, Woda C, Sugimoto H and Kalluri R: Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 19:1047–1053. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Loeffler I, Liebisch M, Allert S, Kunisch E, Kinne RW and Wolf G: FSP1-specific SMAD2 knockout in renal tubular, endothelial, and interstitial cells reduces fibrosis and epithelial-to-mesenchymal transition in murine STZ-induced diabetic nephropathy. Cell Tissue Res. 372:115–133. 2018. View Article : Google Scholar : PubMed/NCBI

52 

Lv W, Booz GW, Wang Y, Fan F and Roman RJ: Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets. Eur J Pharmacol. 820:65–76. 2018. View Article : Google Scholar : PubMed/NCBI

53 

Li MO and Flavell RA: TGF-beta: A master of all T cell trades. Cell. 134:392–404. 2008. View Article : Google Scholar : PubMed/NCBI

54 

Li MO, Wan YY, Sanjabi S, Robertson AKL and Flavell RA: Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 24:99–146. 2006. View Article : Google Scholar : PubMed/NCBI

55 

Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM and Karlsson S: Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA. 90:770–774. 1993. View Article : Google Scholar : PubMed/NCBI

56 

Yaswen L, Kulkarni AB, Fredrickson T, Mittleman B, Schiffman R, Payne S, Longenecker G, Mozes E and Karlsson S: Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse. Blood. 87:1439–1445. 1996. View Article : Google Scholar : PubMed/NCBI

57 

Werner F, Jain MK, Feinberg MW, Sibinga NE, Pellacani A, Wiesel P, Chin MT, Topper JN, Perrella MA and Lee ME: Transforming growth factor-beta 1 inhibition of macrophage activation is mediated via Smad3. J Biol Chem. 275:36653–36658. 2000. View Article : Google Scholar : PubMed/NCBI

58 

Martinez GJ, Zhang Z, Chung Y, Reynolds JM, Lin X, Jetten AM, Feng XH and Dong C: Smad3 differentially regulates the induction of regulatory and inflammatory T cell differentiation. J Biol Chem. 284:35283–35286. 2009. View Article : Google Scholar : PubMed/NCBI

59 

Zhang F, Tsai S, Kato K, Yamanouchi D, Wang C, Rafii S, Liu B and Kent KC: Transforming growth factor-beta promotes recruitment of bone marrow cells and bone marrow-derived mesenchymal stem cells through stimulation of MCP-1 production in vascular smooth muscle cells. J Biol Chem. 284:17564–17574. 2009. View Article : Google Scholar : PubMed/NCBI

60 

Zhang YY, Tang PM, Tang PC, Xiao J, Huang XR, Yu C, Ma RCW and Lan HY: LRNA9884, a Novel Smad3-Dependent long noncoding rna, promotes diabetic kidney injury in db/db Mice via Enhancing MCP-1-Dependent renal inflammation. Diabetes. 68:1485–1498. 2019. View Article : Google Scholar : PubMed/NCBI

61 

Zhou Q, Huang XR, Yu J, Yu X and Lan HY: Long Noncoding RNA Arid2-IR Is a Novel Therapeutic Target for Renal Inflammation. Mol Ther. 23:1034–1043. 2015. View Article : Google Scholar : PubMed/NCBI

62 

Wang W, Huang XR, Li AG, Liu F, Li JH, Truong LD, Wang XJ and Lan HY: Signaling mechanism of TGF-beta1 in prevention of renal inflammation: Role of Smad7. J Am Soc Nephrol. 16:1371–1383. 2005. View Article : Google Scholar : PubMed/NCBI

63 

Lan HY: Smad7 as a therapeutic agent for chronic kidney diseases. Front Biosci. 13:4984–4992. 2008. View Article : Google Scholar : PubMed/NCBI

64 

Chung AC, Huang XR, Zhou L, Heuchel R, Lai KN and Lan HY: Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice. Nephrol Dial Transplant. 24:1443–1454. 2009. View Article : Google Scholar : PubMed/NCBI

65 

You YK, Wu WF, Huang XR, Li HD, Ren YP, Zeng JC, Chen H and Lan HY: Deletion of Smad3 protects against C-reactive protein-induced renal fibrosis and inflammation in obstructive nephropathy. Int J Biol Sci. 17:3911–3922. 2021. View Article : Google Scholar : PubMed/NCBI

66 

Liu Z, Huang XR, Chen HY, Fung E, Liu J and Lan HY: Deletion of angiotensin-converting enzyme-2 promotes hypertensive nephropathy by targeting Smad7 for ubiquitin degradation. Hypertension. 70:822–830. 2017. View Article : Google Scholar : PubMed/NCBI

67 

Wang Y, Wang Y, Yang M and Ma X: Implication of cellular senescence in the progression of chronic kidney disease and the treatment potencies. Biomed Pharmacother. 135:1111912021. View Article : Google Scholar : PubMed/NCBI

68 

Zhang JQ, Li YY, Zhang XY, Tian ZH, Liu C, Wang ST and Zhang FR: Cellular senescence of renal tubular epithelial cells in renal fibrosis. Front Endocrinol (Lausanne). 14:10856052023. View Article : Google Scholar : PubMed/NCBI

69 

Li C, Shen Y, Huang L, Liu C and Wang J: Senolytic therapy ameliorates renal fibrosis postacute kidney injury by alleviating renal senescence. FASEB J. 35:e212292021.PubMed/NCBI

70 

Lyu G, Guan Y, Zhang C, Zong L, Sun L, Huang X, Huang L, Zhang L, Tian XL, Zhou Z and Tao W: TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging. Nat Commun. 9:25602018. View Article : Google Scholar : PubMed/NCBI

71 

Ni JY, Wang X, Xie HY, Yang NH, Li JY, Sun XA, Guo HJ, Zhou L, Zhang W, Liu J and Lu LM: Deubiquitinating enzyme USP11 promotes renal tubular cell senescence and fibrosis via inhibiting the ubiquitin degradation of TGF-β receptor II. Acta Pharmacol Sin. 44:584–595. 2023. View Article : Google Scholar : PubMed/NCBI

72 

Ueda S, Tominaga T, Ochi A, Sakurai A, Nishimura K, Shibata E, Wakino S, Tamaki M and Nagai K: TGF-β1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction. Sci Rep. 11:216432021. View Article : Google Scholar : PubMed/NCBI

73 

Tang C, Livingston MJ, Liu Z and Dong Z: Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 16:489–508. 2020. View Article : Google Scholar : PubMed/NCBI

74 

Yang C, Chen XC, Li ZH, Wu HL, Jing KP, Huang XR, Ye L, Wei B, Lan HY and Liu HF: SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy. Autophagy. 17:2325–2344. 2021. View Article : Google Scholar : PubMed/NCBI

75 

Zehender A, Li YN, Lin NY, Stefanica A, Nüchel J, Chen CW, Hsu HH, Zhu H, Ding X, Huang J, et al: TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy. Nat Commun. 12:44042021. View Article : Google Scholar : PubMed/NCBI

76 

Sanz AB, Sanchez-Niño MD, Ramos AM and Ortiz A: Regulated cell death pathways in kidney disease. Nat Rev Nephrol. 19:281–299. 2023. View Article : Google Scholar : PubMed/NCBI

77 

Massagué J, Blain SW and Lo RS: TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 103:295–309. 2000. View Article : Google Scholar : PubMed/NCBI

78 

Wang W, Chen J, Hu D, Pan P, Liang L, Wu W, Tang Y, Huang XR, Yu X, Wu J and Lan HY: SARS-CoV-2 N protein induces acute kidney injury via Smad3-Dependent G1 cell cycle arrest mechanism. Adv Sci (Weinh). 9:e21032482022. View Article : Google Scholar : PubMed/NCBI

79 

Fu S, Tang Y, Huang XR, Feng M, Xu AP and Lan HY: Smad7 protects against acute kidney injury by rescuing tubular epithelial cells from the G1 cell cycle arrest. Clin Sci (Lond). 131:1955–1969. 2017. View Article : Google Scholar : PubMed/NCBI

80 

Zhang HY, Cheng M, Zhang L and Wang YP: Ferroptosis and renal fibrosis: A new target for the future (Review). Exp Ther Med. 25:132022. View Article : Google Scholar : PubMed/NCBI

81 

Wang J, Wang Y, Liu Y, Cai X, Huang X, Fu W, Wang L, Qiu L, Li J and Sun L: Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model. Cell Death Discov. 8:1272022. View Article : Google Scholar : PubMed/NCBI

82 

Wang JN, Yang Q, Yang C, Cai YT, Xing T, Gao L, Wang F, Chen X, Liu XQ, He XY, et al: Smad3 promotes AKI sensitivity in diabetic mice via interaction with p53 and induction of NOX4-dependent ROS production. Redox Biol. 32:1014792020. View Article : Google Scholar : PubMed/NCBI

83 

Li J, Yang J, Xian Q, Su H, Ni Y and Wang L: Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis. Phytother Res. Mar 15–2024.(Epub ahead of print). View Article : Google Scholar

84 

Zhu B, Ni Y, Gong Y, Kang X, Guo H, Liu X, Li J and Wang L: Formononetin ameliorates ferroptosis-associated fibrosis in renal tubular epithelial cells and in mice with chronic kidney disease by suppressing the Smad3/ATF3/SLC7A11 signaling. Life Sci. 315:1213312023. View Article : Google Scholar : PubMed/NCBI

85 

Streets A and Ong A: Post-translational modifications of the polycystin proteins. Cell Signal. 72:1096442020. View Article : Google Scholar : PubMed/NCBI

86 

Duan G and Walther D: The roles of post-translational modifications in the context of protein interaction networks. PLoS Comput Biol. 11:e10040492015. View Article : Google Scholar : PubMed/NCBI

87 

Xu P, Liu J and Derynck R: Post-translational regulation of TGF-β receptor and Smad signaling. FEBS Lett. 586:1871–1884. 2012. View Article : Google Scholar : PubMed/NCBI

88 

Huse M, Muir TW, Xu L, Chen YG, Kuriyan J and Massagué J: The TGF beta receptor activation process: An inhibitor- to substrate-binding switch. Mol Cell. 8:671–682. 2001. View Article : Google Scholar : PubMed/NCBI

89 

Shi Y and Massagué J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI

90 

Xu P, Lin X and Feng XH: Posttranslational Regulation of Smads. Cold Spring Harb Perspect Biol. 8:a0220872016. View Article : Google Scholar : PubMed/NCBI

91 

Adhikary L, Chow F, Nikolic-Paterson DJ, Stambe C, Dowling J, Atkins RC and Tesch GH: Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy. Diabetologia. 47:1210–1222. 2004. View Article : Google Scholar : PubMed/NCBI

92 

De Borst MH, Prakash J, Melenhorst WB, van den Heuvel MC, Kok RJ, Navis G and van Goor H: Glomerular and tubular induction of the transcription factor c-Jun in human renal disease. J Pathol. 213:219–228. 2007. View Article : Google Scholar : PubMed/NCBI

93 

Ma FY, Sachchithananthan M, Flanc RS and Nikolic-Paterson DJ: Mitogen activated protein kinases in renal fibrosis. Front Biosci (Schol Ed). 1:171–187. 2009. View Article : Google Scholar : PubMed/NCBI

94 

Stambe C, Atkins RC, Tesch GH, Masaki T, Schreiner GF and Nikolic-Paterson DJ: The role of p38alpha mitogen-activated protein kinase activation in renal fibrosis. J Am Soc Nephrol. 15:370–379. 2004. View Article : Google Scholar : PubMed/NCBI

95 

Ma FY, Flanc RS, Tesch GH, Bennett BL, Friedman GC and Nikolic-Paterson DJ: Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab Invest. 89:470–484. 2009. View Article : Google Scholar : PubMed/NCBI

96 

Müller R, Daniel C, Hugo C, Amann K, Mielenz D, Endlich K, Braun T, van der Veen B, Heeringa P, Schett G and Zwerina J: The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis. PLoS One. 8:e563162013. View Article : Google Scholar : PubMed/NCBI

97 

Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu S, Zheng W, Little PJ and Osman N: Transforming growth factor-β signalling: Role and consequences of Smad linker region phosphorylation. Cell Signal. 25:2017–2024. 2013. View Article : Google Scholar : PubMed/NCBI

98 

Yang F, Chung ACK, Huang XR and Lan HY: Angiotensin II induces connective tissue growth factor and collagen I expression via transforming growth factor-beta-dependent and -independent Smad pathways: The role of Smad3. Hypertension. 54:877–884. 2009. View Article : Google Scholar : PubMed/NCBI

99 

Chung AC, Zhang H, Kong YZ, Tan JJ, Huang XR, Kopp JB and Lan HY: Advanced glycation end-products induce tubular CTGF via TGF-beta-independent Smad3 signaling. J Am Soc Nephrol. 21:249–260. 2010. View Article : Google Scholar : PubMed/NCBI

100 

You YK, Huang XR, Chen HY, Lyu XF, Liu HF and Lan HY: C-Reactive protein promotes diabetic kidney disease in db/db Mice via the CD32b-Smad3-mTOR signaling pathway. Sci Rep. 6:267402016. View Article : Google Scholar : PubMed/NCBI

101 

Chen X, Wang H, Liao HJ, Hu W, Gewin L, Mernaugh G, Zhang S, Zhang ZY, Vega-Montoto L, Vanacore RM, et al: Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling. J Clin Invest. 124:3295–3310. 2014. View Article : Google Scholar : PubMed/NCBI

102 

Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi F, et al: PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 125:915–928. 2006. View Article : Google Scholar : PubMed/NCBI

103 

Samarakoon R, Rehfuss A, Khakoo NS, Falke LL, Dobberfuhl AD, Helo S, Overstreet JM, Goldschmeding R and Higgins PJ: Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair. FASEB J. 30:3308–3320. 2016. View Article : Google Scholar : PubMed/NCBI

104 

Inoue K, Matsui I, Hamano T, Fujii N, Shimomura A, Nakano C, Kusunoki Y, Takabatake Y, Hirata M, Nishiyama A, et al: Maxacalcitol ameliorates tubulointerstitial fibrosis in obstructed kidneys by recruiting PPM1A/VDR complex to pSmad3. Lab Invest. 92:1686–1697. 2012. View Article : Google Scholar : PubMed/NCBI

105 

Tang J, Goldschmeding R, Samarakoon R and Higgins PJ: Protein phosphatase Mg2+/Mn2+ dependent-1A and PTEN deregulation in renal fibrosis: Novel mechanisms and co-dependency of expression. FASEB J. 34:2641–2656. 2020. View Article : Google Scholar : PubMed/NCBI

106 

Meyer-Schwesinger C: The ubiquitin-proteasome system in kidney physiology and disease. Nat Rev Nephrol. 15:393–411. 2019. View Article : Google Scholar : PubMed/NCBI

107 

Tan R, He W, Lin X, Kiss LP and Liu Y: Smad ubiquitination regulatory factor-2 in the fibrotic kidney: Regulation, target specificity, and functional implication. Am J Physiol Renal Physiol. 294:F1076–F1083. 2008. View Article : Google Scholar : PubMed/NCBI

108 

Iyengar PV: Regulation of ubiquitin enzymes in the TGF-β Pathway. Int J Mol Sci. 18:8772017. View Article : Google Scholar : PubMed/NCBI

109 

Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K and Wrana JL: TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol. 3:587–595. 2001. View Article : Google Scholar : PubMed/NCBI

110 

Wang L, Zha H, Huang J and Shi L: Flavin containing monooxygenase 2 regulates renal tubular cell fibrosis and paracrine secretion via SMURF2 in AKI-CKD transformation. Int J Mol Med. 52:1102023. View Article : Google Scholar : PubMed/NCBI

111 

Liu FY, Li XZ, Peng YM, Liu H and Liu YH: Arkadia-Smad7-mediated positive regulation of TGF-beta signaling in a rat model of tubulointerstitial fibrosis. Am J Nephrol. 27:176–183. 2007. View Article : Google Scholar : PubMed/NCBI

112 

Liu FY and Li XZ: The roles of Arkadia in renal tubular epithelial to mesenchymal transition. Med Hypotheses. 67:1205–1207. 2006. View Article : Google Scholar : PubMed/NCBI

113 

Wu W, Huang XR, You Y, Xue L, Wang XJ, Meng X, Lin X, Shen J, Yu X, Lan HY and Chen H: Latent TGF-β1 protects against diabetic kidney disease via Arkadia/Smad7 signaling. Int J Biol Sci. 17:3583–3594. 2021. View Article : Google Scholar : PubMed/NCBI

114 

Gao S, Alarcón C, Sapkota G, Rahman S, Chen PY, Goerner N, Macias MJ, Erdjument-Bromage H, Tempst P and Massagué J: Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 36:457–468. 2009. View Article : Google Scholar : PubMed/NCBI

115 

Manning JA, Shah SS, Nikolic A, Henshall TL, Khew-Goodall Y and Kumar S: The ubiquitin ligase NEDD4-2/NEDD4L regulates both sodium homeostasis and fibrotic signaling to prevent end-stage renal disease. Cell Death Dis. 12:3982021. View Article : Google Scholar : PubMed/NCBI

116 

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

117 

Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK and Bernards R: A genomic and functional inventory of deubiquitinating enzymes. Cell. 123:773–786. 2005. View Article : Google Scholar : PubMed/NCBI

118 

Zhang J, Zhang X, Xie F, Zhang Z, van Dam H, Zhang L and Zhou F: The regulation of TGF-β/SMAD signaling by protein deubiquitination. Protein Cell. 5:503–517. 2014. View Article : Google Scholar : PubMed/NCBI

119 

Komander D, Clague MJ and Urbé S: Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol. 10:550–563. 2009. View Article : Google Scholar : PubMed/NCBI

120 

Soji K, Doi S, Nakashima A, Sasaki K, Doi T and Masaki T: Deubiquitinase inhibitor PR-619 reduces Smad4 expression and suppresses renal fibrosis in mice with unilateral ureteral obstruction. PLoS One. 13:e02024092018. View Article : Google Scholar : PubMed/NCBI

121 

Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, et al: FAM/USP9×, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 136:123–135. 2009. View Article : Google Scholar : PubMed/NCBI

122 

Xie S, Xing Y, Shi W, Zhang M, Chen M, Fang W, Liu S, Zhang T, Zeng X, Chen S, et al: Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia-reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination. Acta Pharm Sin B. 12:4138–4153. 2022. View Article : Google Scholar : PubMed/NCBI

123 

Liao X, Li Y, Liu J, Zhang Y, Tan J, Kass DJ, Rojas M, Mallampalli RK, Zhao J and Zhao Y: Deubiquitinase USP13 promotes extracellular matrix expression by stabilizing Smad4 in lung fibroblast cells. Transl Res. 223:15–24. 2020. View Article : Google Scholar : PubMed/NCBI

124 

Song C, Liu W and Li J: USP17 is upregulated in osteosarcoma and promotes cell proliferation, metastasis, and epithelial-mesenchymal transition through stabilizing SMAD4. Tumour Biol. 39:10104283177171382017. View Article : Google Scholar : PubMed/NCBI

125 

Zhao Y, Chen X, Lin Y, Li Z, Su X, Fan S, Chen Y, Wang X and Liang G: USP25 inhibits renal fibrosis by regulating TGFβ-SMAD signaling pathway in Ang II-induced hypertensive mice. Biochim Biophys Acta Mol Basis Dis. 1869:1667132023. View Article : Google Scholar : PubMed/NCBI

126 

Sun XH, Xiao HM, Zhang M, Lin ZY, Yang Y, Chen R, Liu PQ, Huang KP and Huang HQ: USP9X deubiquitinates connexin43 to prevent high glucose-induced epithelial-to-mesenchymal transition in NRK-52E cells. Biochem Pharmacol. 188:1145622021. View Article : Google Scholar : PubMed/NCBI

127 

Huang K and Zhao X: USP9X prevents AGEs-induced upregulation of FN and TGF-β1 through activating Nrf2-ARE pathway in rat glomerular mesangial cells. Exp Cell Res. 393:1121002020. View Article : Google Scholar : PubMed/NCBI

128 

Gao F, Qian M, Liu G, Ao W, Dai D and Yin C: USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway. J Inflamm (Lond). 18:252021. View Article : Google Scholar : PubMed/NCBI

129 

Huang Z, Shen S, Wang M, Li W, Wu G, Huang W, Luo W and Liang G: Mouse endothelial OTUD1 promotes angiotensin II-induced vascular remodeling by deubiquitinating SMAD3. EMBO Rep. 24:e561352023. View Article : Google Scholar : PubMed/NCBI

130 

Huang YT, Cheng AC, Tang HC, Huang GC, Cai L, Lin TH, Wu KJ, Tseng PH, Wang GG and Chen WY: USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer. Cell Death Dis. 12:8802021. View Article : Google Scholar : PubMed/NCBI

131 

Wicks SJ, Haros K, Maillard M, Song L, Cohen RE, Dijke PT and Chantry A: The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling. Oncogene. 24:8080–8084. 2005. View Article : Google Scholar : PubMed/NCBI

132 

Tian Y, Liao F and Wu G, Chang D, Yang Y, Dong X, Zhang Z, Zhang Y and Wu G: Ubiquitination and regulation of Smad7 in the TGF-β1/Smad signaling of aristolochic acid nephropathy. Toxicol Mech Methods. 25:645–652. 2015. View Article : Google Scholar : PubMed/NCBI

133 

Zhao Y, Thornton AM, Kinney MC, Ma CA, Spinner JJ, Fuss IJ, Shevach EM and Jain A: The Deubiquitinase CYLD targets Smad7 protein to regulate transforming growth factor β (TGF-β) signaling and the development of regulatory T cells. J Biol Chem. 286:40520–40530. 2011. View Article : Google Scholar : PubMed/NCBI

134 

Wang B, Xu X, Yang Z, Zhang L and Liu Y, Ma A, Xu G, Tang M, Jing T, Wu L and Liu Y: POH1 contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-β receptors and caveolin-1. EBioMedicine. 41:320–332. 2019. View Article : Google Scholar : PubMed/NCBI

135 

Shi Y, Tao M, Chen H, Ma X, Wang Y, Hu Y, Zhou X, Li J, Cui B, Qiu A, et al: Ubiquitin-specific protease 11 promotes partial epithelial-to-mesenchymal transition by deubiquitinating the epidermal growth factor receptor during kidney fibrosis. Kidney Int. 103:544–564. 2023. View Article : Google Scholar : PubMed/NCBI

136 

Jacko AM, Nan L, Li S, Tan J, Zhao J, Kass DJ and Zhao Y: De-ubiquitinating enzyme, USP11, promotes transforming growth factor β-1 signaling through stabilization of transforming growth factor β receptor II. Cell Death Dis. 7:e24742016. View Article : Google Scholar : PubMed/NCBI

137 

Du C, Chen X, Su Q, Lu W, Wang Q, Yuan H, Zhang Z, Wang X, Wu H and Qi Y: The function of SUMOylation and Its critical roles in cardiovascular diseases and potential clinical implications. Int J Mol Sci. 22:106182021. View Article : Google Scholar : PubMed/NCBI

138 

Wang X, Liu T, Huang Y, Dai Y and Lin H: Regulation of transforming growth factor-beta signalling by SUMOylation and its role in fibrosis. Open Biol. 11:2100432021. View Article : Google Scholar : PubMed/NCBI

139 

Kang JS, Saunier EF, Akhurst RJ and Derynck R: The type I TGF-beta receptor is covalently modified and regulated by sumoylation. Nat Cell Biol. 10:654–664. 2008. View Article : Google Scholar : PubMed/NCBI

140 

Enserink JM: Sumo and the cellular stress response. Cell Div. 10:42015. View Article : Google Scholar : PubMed/NCBI

141 

Reverter D and Lima CD: A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex. Structure. 12:1519–1531. 2004. View Article : Google Scholar : PubMed/NCBI

142 

Gong L and Yeh ETH: Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3. J Biol Chem. 281:15869–15877. 2006. View Article : Google Scholar : PubMed/NCBI

143 

Tan M, Zhang D, Zhang E, Xu D, Liu Z, Qiu J, Fan Y and Shen B: SENP2 suppresses epithelial-mesenchymal transition of bladder cancer cells through deSUMOylation of TGF-βRI. Mol Carcinog. 56:2332–2341. 2017. View Article : Google Scholar : PubMed/NCBI

144 

Long J, Wang G, He D and Liu F: Repression of Smad4 transcriptional activity by SUMO modification. Biochem J. 379((Pt 1)): 23–29. 2004. View Article : Google Scholar : PubMed/NCBI

145 

Zhou X, Gao C, Huang W, Yang M, Chen G, Jiang L, Gou F, Feng H, Ai N and Xu Y: High glucose induces sumoylation of Smad4 via SUMO2/3 in mesangial cells. Biomed Res Int. 2014:7826252014. View Article : Google Scholar : PubMed/NCBI

146 

Liu P, Zhang J, Wang Y, Wang C, Qiu X and Chen DQ: Natural products against renal fibrosis via modulation of SUMOylation. Front Pharmacol. 13:8008102022. View Article : Google Scholar : PubMed/NCBI

147 

Liu W, Yuan Q, Cao S, Wang G, Liu X, Xia Y, Bian Y, Xu F and Chen Y: Review: Acetylation mechanisms and targeted therapies in cardiac fibrosis. Pharmacol Res. 193:1068152023. View Article : Google Scholar : PubMed/NCBI

148 

Bugyei-Twum A, Advani A, Advani SL, Zhang Y, Thai K, Kelly DJ and Connelly KA: High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy. Cardiovasc Diabetol. 13:892014. View Article : Google Scholar : PubMed/NCBI

149 

Inoue Y, Itoh Y, Abe K, Okamoto T, Daitoku H, Fukamizu A, Onozaki K and Hayashi H: Smad3 is acetylated by p300/CBP to regulate its transactivation activity. Oncogene. 26:500–508. 2007. View Article : Google Scholar : PubMed/NCBI

150 

Rai R, Verma SK, Kim D, Ramirez V, Lux E, Li C, Sahoo S, Wilsbacher LD, Vaughan DE, Quaggin SE and Ghosh AK: A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis. Epigenetics. 12:1004–1013. 2017. View Article : Google Scholar : PubMed/NCBI

151 

Morigi M, Perico L and Benigni A: Sirtuins in renal health and disease. J Am Soc Nephrol. 29:1799–1809. 2018. View Article : Google Scholar : PubMed/NCBI

152 

Huang XZ, Wen D, Zhang M, Xie Q, Ma L, Guan Y, Ren Y, Chen J and Hao CM: Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-β/Smad3 pathway. J Cell Biochem. 115:996–1005. 2014. View Article : Google Scholar : PubMed/NCBI

153 

Chen Q, Zeng Y, Yang X, Wu Y, Zhang S, Huang S, Zhong Y and Chen M: Resveratrol ameliorates myocardial fibrosis by regulating Sirt1/Smad3 deacetylation pathway in rat model with dilated cardiomyopathy. BMC Cardiovasc Disord. 22:172022. View Article : Google Scholar : PubMed/NCBI

154 

Simic P, Williams EO, Bell EL, Gong JJ, Bonkowski M and Guarente L: SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis. Cell Rep. 3:1175–1186. 2013. View Article : Google Scholar : PubMed/NCBI

155 

Yang S, Yang G, Wang X, Xiang J, Kang L and Liang Z: SIRT2 alleviated renal fibrosis by deacetylating SMAD2 and SMAD3 in renal tubular epithelial cells. Cell Death Dis. 14:6462023. View Article : Google Scholar : PubMed/NCBI

156 

Ma J and Hart GW: O-GlcNAc profiling: From proteins to proteomes. Clin Proteomics. 11:82014. View Article : Google Scholar : PubMed/NCBI

157 

Harosh-Davidovich SB and Khalaila I: O-GlcNAcylation affects β-catenin and E-cadherin expression, cell motility and tumorigenicity of colorectal cancer. Exp Cell Res. 364:42–49. 2018. View Article : Google Scholar : PubMed/NCBI

158 

He XF, Hu X, Wen GJ, Wang Z and Lin WJ: O-GlcNAcylation in cancer development and immunotherapy. Cancer Lett. 566:2162582023. View Article : Google Scholar : PubMed/NCBI

159 

Ma J and Hart GW: Protein O-GlcNAcylation in diabetes and diabetic complications. Expert Rev Proteomics. 10:365–380. 2013. View Article : Google Scholar : PubMed/NCBI

160 

Park J, Lai MKP, Arumugam TV and Jo DG: O-GlcNAcylation as a therapeutic target for Alzheimer's disease. Neuromolecular Med. 22:171–193. 2020. View Article : Google Scholar : PubMed/NCBI

161 

Feng D, Sheng-Dong L, Tong W and Zhen-Xian D: O-GlcNAcylation of RAF1 increases its stabilization and induces the renal fibrosis. Biochim Biophys Acta Mol Basis Dis. 1866:1655562020. View Article : Google Scholar : PubMed/NCBI

162 

Kim YJ, Kang MJ, Kim E, Kweon TH, Park YS, Ji S, Yang WH, Yi EC and Cho JW: O-GlcNAc stabilizes SMAD4 by inhibiting GSK-3β-mediated proteasomal degradation. Sci Rep. 10:199082020. View Article : Google Scholar : PubMed/NCBI

163 

Yuan M, Song ZH, Ying MD, Zhu H, He QJ, Yang B and Cao J: N-myristoylation: From cell biology to translational medicine. Acta Pharmacol Sin. 41:1005–1015. 2020. View Article : Google Scholar : PubMed/NCBI

164 

Stockwell BR and Schreiber SL: TGF-beta-signaling with small molecule FKBP12 antagonists that bind myristoylated FKBP12-TGF-beta type I receptor fusion proteins. Chem Biol. 5:385–395. 1998. View Article : Google Scholar : PubMed/NCBI

165 

Zhu F, Xie N, Jiang Z, Li G, Ma L and Tong T: The cellular senescence-inhibited gene is essential for PPM1A myristoylation to modulate transforming growth factor β signaling. Mol Cell Biol. 38:e00414–18. 2018. View Article : Google Scholar : PubMed/NCBI

166 

Al-Salihi MA, Herhaus L, Macartney T and Sapkota GP: USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol. 2:1200632012. View Article : Google Scholar : PubMed/NCBI

167 

Siwy J, Mischak H and Zürbig P: Proteomics and personalized medicine: A focus on kidney disease. Expert Rev Proteomics. 16:773–782. 2019. View Article : Google Scholar : PubMed/NCBI

168 

Giudice G and Petsalaki E: Proteomics and phosphoproteomics in precision medicine: Applications and challenges. Brief Bioinform. 20:767–777. 2019. View Article : Google Scholar : PubMed/NCBI

169 

Xu H, Wu T and Huang L: Therapeutic and delivery strategies of phytoconstituents for renal fibrosis. Adv Drug Deliv Rev. 177:1139112021. View Article : Google Scholar : PubMed/NCBI

170 

Trac N, Ashraf A, Giblin J, Prakash S, Mitragotri S and Chung EJ: Spotlight on genetic kidney diseases: A call for drug delivery and nanomedicine solutions. ACS Nano. 17:6165–6177. 2023. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li J, Zou Y, Kantapan J, Su H, Wang L and Dechsupa N: TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review). Mol Med Rep 30: 143, 2024.
APA
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., & Dechsupa, N. (2024). TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review). Molecular Medicine Reports, 30, 143. https://doi.org/10.3892/mmr.2024.13267
MLA
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., Dechsupa, N."TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review)". Molecular Medicine Reports 30.2 (2024): 143.
Chicago
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., Dechsupa, N."TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review)". Molecular Medicine Reports 30, no. 2 (2024): 143. https://doi.org/10.3892/mmr.2024.13267
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Zou Y, Kantapan J, Su H, Wang L and Dechsupa N: TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review). Mol Med Rep 30: 143, 2024.
APA
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., & Dechsupa, N. (2024). TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review). Molecular Medicine Reports, 30, 143. https://doi.org/10.3892/mmr.2024.13267
MLA
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., Dechsupa, N."TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review)". Molecular Medicine Reports 30.2 (2024): 143.
Chicago
Li, J., Zou, Y., Kantapan, J., Su, H., Wang, L., Dechsupa, N."TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review)". Molecular Medicine Reports 30, no. 2 (2024): 143. https://doi.org/10.3892/mmr.2024.13267
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