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Article Open Access

Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15

  • Authors:
    • Mingcong Huang
    • Jing Chang
    • Yu Liu
    • Jiming Yin
    • Xiangjun Zeng
  • View Affiliations / Copyright

    Affiliations: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China, Department of Physiology, Beijing You An Hospital, Capital Medical University, Beijing 100069, P.R. China, Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China, Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 122
    |
    Published online on: March 7, 2025
       https://doi.org/10.3892/mmr.2025.13487
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Abstract

Glomerular basement membrane (GBM) thickening, the earliest morphological change of diabetic nephropathy (DN), is related to glomerular endothelial cells (GECs) dysfunction which increase extracellular matrix (ECM) synthesizing. Apelin, the endogenous ligand for apelin/apelin receptor (APJ), is reported to alleviate endothelial cell dysfunction in DN. Therefore, it was hypothesized that apelin/APJ reduced GBM thickening by decreasing the synthesis of ECM in GECs. The results showed that apelin reduced glomerular fibrosis and GBM thickening by decreasing the expression of laminin and collagen IV in diabetic mice, which were cancelled following APJ knockout in GECs. Furthermore, apelin/APJ inhibited the synthesis of laminin and collagen IV in GECs by increasing the expression and activity of SIRT3, which promoted KLF15 deacetylation and translocation into nucleus. In conclusion, apelin/APJ reduced GBM thickening in diabetes mellitus by preventing laminin and collagen IV synthesizing via SIRT3‑KLF15 pathway in GECs.
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1 

Papadopoulou-Marketou N, Chrousos GP and Kanaka-Gantenbein C: Diabetic nephropathy in type 1 diabetes: A review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev. 33:28412017. View Article : Google Scholar : PubMed/NCBI

2 

Alicic RZ, Rooney MT and Tuttle KR: Diabetic kidney disease: Challenges, progress, and possibilities. Clin J Am Soc Nephrol. 7:2032–2045. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Naylor RW, Morais MRPT and Lennon R: Complexities of the glomerular basement membrane. Nat Rev Nephrol. 17:112–127. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Marshall CB: Rethinking glomerular basement membrane thickening in diabetic nephropathy: Adaptive or pathogenic? Am J Physiol Renal Physiol. 311:F831–F843. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Tuleta I and Frangogiannis NG: Diabetic fibrosis. Biochim Biophys Acta Mol Basis. 1867:1660442021. View Article : Google Scholar : PubMed/NCBI

6 

Petrazzuolo A, Sabiu G, Assi E, Maestroni A, Pastore I, Lunati ME, Montefusco L, Loretelli C, Rossi G, Ben Nasr M, et al: Broadening horizons in mechanisms, management, and treatment of diabetic kidney disease. Pharmacol Res. 190:106710:2021.

7 

St John PL and Abrahamson DR: Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and −11 chains. Kidney Int. 60:1037–1046. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Kriz W, Löwen J, Federico G, van den Born J, Gröne E and Gröne HJ: Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy. Am J Physiol Renal Physiol. 312:F1101–F1111. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Stefan G, Stancu S, Zugravu A, Petre N, Mandache E and Mircescu G: Histologic predictors of renal outcome in diabetic nephropathy: Beyond renal pathology society classification. Medicine (Baltimore). 98:e163332019. View Article : Google Scholar : PubMed/NCBI

10 

Lenoir O, Jasiek M, Hénique C, Guyonnet L, Hartleben B, Bork T, Chipont A, Flosseau K, Bensaada I, Schmitt A, et al: Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy. 11:1130–1145. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Wardle EN: How does hyperglycaemia predispose to diabetic nephropathy? QJM. 89:943–951. 1996. View Article : Google Scholar : PubMed/NCBI

12 

DeFronzo RA, Reeves WB and Awad AS: Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat Rev Nephrol. 17:319–334. 2021. View Article : Google Scholar : PubMed/NCBI

13 

Eringa EC, Serne EH, Meijer RI, Schalkwijk CG, Houben AJ, Stehouwer CD, Smulders YM and van Hinsbergh VW: Endothelial dysfunction in (pre) diabetes: Characteristics, causative mechanisms and pathogenic role in type 2 diabetes. Rev Endocr Metab Disord. 14:39–48. 2013. View Article : Google Scholar : PubMed/NCBI

14 

El Husseny MW, Mamdouh M, Shaban S, Ibrahim Abushouk A, Zaki MM, Ahmed OM and Abdel-Daim MM: Adipokines: Potential therapeutic targets for vascular dysfunction in type II Diabetes mellitus and obesity. J Diabetes Res. 2017:80959262017. View Article : Google Scholar : PubMed/NCBI

15 

Kim S, Kim S, Hwang AR, Choi HC, Lee JY and Woo CH: Apelin-13 inhibits methylglyoxal-induced unfolded protein responses and endothelial dysfunction via regulating AMPK pathway. Int J Mol Sci. 21:40692020. View Article : Google Scholar : PubMed/NCBI

16 

Cheng J, Luo X, Huang Z and Chen L: Apelin/APJ system: A potential therapeutic target for endothelial dysfunction-related diseases. J Cell Physiol. 234:12149–12160. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Mariappan MM: Signaling mechanisms in the regulation of renal matrix metabolism in diabetes. Exp Diabetes Res. 2012:7498122012. View Article : Google Scholar : PubMed/NCBI

18 

Ni T, Lin N, Huang X, Lu W, Sun Z, Zhang J, Lin H, Chi J and Guo H: Icariin ameliorates diabetic cardiomyopathy through apelin/sirt3 signalling to improve mitochondrial dysfunction. Front Pharmacol. 11:2562020. View Article : Google Scholar : PubMed/NCBI

19 

Guan YM, Diao ZL, Huang HD, Zheng JF, Zhang QD, Wang LY and Liu WH: Bioactive peptide apelin rescues acute kidney injury by protecting the function of renal tubular mitochondria. Amino Acids. 53:1229–1240. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Li N, Zhang J, Yan X, Zhang C, Liu H, Shan X, Li J, Yang Y, Huang C, Zhang P, et al: SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension. Oncotarget. 8:39592–39604. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Rane MJ, Zhao Y and Cai L: Krϋppel-like factors (KLFs) in renal physiology and disease. EBioMedicine. 40:743–750. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Gao X, Huang L, Grosjean F, Esposito V, Wu J, Fu L, Hu H, Tan J, He C, Gray S, et al: Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: A role for KLF15. Kidney Int. 79:987–996. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, Ferrario F, Fogo AB, Haas M, de Heer E, et al: Renal pathology society. pathologic classification of diabetic nephropathy. J Am Soc Nephrol. 21:556–563. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Wang Y, Zhang R, Shen H, Kong J and Lv X: Pioglitazone protects blood vessels through inhibition of the apelin signaling pathway by promoting KLF4 expression in rat models of T2DM. Biosci Rep. 39:BSR201903172019. View Article : Google Scholar : PubMed/NCBI

26 

Yin J, Wang Y, Chang J, Li B, Zhang J, Liu Y, Lai S, Jiang Y, Li H and Zeng X: Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i. Cell Death Dis. 9:10312018. View Article : Google Scholar : PubMed/NCBI

27 

Abrahamson DR: Role of the podocyte (and glomerular endothelium) in building the GBM. Semin Nephrol. 32:342–349. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Lennon R, Byron A, Humphries JD, Randles MJ, Carisey A, Murphy S, Knight D, Brenchley PE, Zent R and Humphries MJ: Global analysis reveals the complexity of the human glomerular extracellular matrix. J Am Soc Nephrol. 25:939–951. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Miner JH: Type IV collagen and diabetic kidney disease. Nat Rev Nephrol. 16:3–4. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Seo K, Parikh VN and Ashley EA: Stretch-induced biased signaling in angiotensin ii type 1 and apelin receptors for the mediation of cardiac contractility and hypertrophy. Front Physiol. 11:1812020. View Article : Google Scholar : PubMed/NCBI

31 

Eleftheriadis T, Antoniadi G, Pissas G, Liakopoulos V and Stefanidis I: The renal endothelium in diabetic nephropathy. Ren Fail. 35:592–599. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Swärd P and Rippe B: Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability. Acta Physiol (Oxf). 204:294–307. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Jaimes EA, Hua P, Tian RX and Raij L: Human glomerular endothelium: Interplay among glucose, free fatty acids, angiotensin II, and oxidative stress. Am J Physiol Renal Physiol. 298:F125–F132. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Li N, Ma X, Ban T, Xu S, Ma Y, Ason B and Hu LA: Loss of APJ mediated β-arrestin signalling improves high-fat diet induced metabolic dysfunction but does not alter cardiac function in mice. Biochem J. 477:3313–3327. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang M, Chang J, Liu Y, Yin J and Zeng X: Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15. Mol Med Rep 31: 122, 2025.
APA
Huang, M., Chang, J., Liu, Y., Yin, J., & Zeng, X. (2025). Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15. Molecular Medicine Reports, 31, 122. https://doi.org/10.3892/mmr.2025.13487
MLA
Huang, M., Chang, J., Liu, Y., Yin, J., Zeng, X."Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15". Molecular Medicine Reports 31.5 (2025): 122.
Chicago
Huang, M., Chang, J., Liu, Y., Yin, J., Zeng, X."Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15". Molecular Medicine Reports 31, no. 5 (2025): 122. https://doi.org/10.3892/mmr.2025.13487
Copy and paste a formatted citation
x
Spandidos Publications style
Huang M, Chang J, Liu Y, Yin J and Zeng X: Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15. Mol Med Rep 31: 122, 2025.
APA
Huang, M., Chang, J., Liu, Y., Yin, J., & Zeng, X. (2025). Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15. Molecular Medicine Reports, 31, 122. https://doi.org/10.3892/mmr.2025.13487
MLA
Huang, M., Chang, J., Liu, Y., Yin, J., Zeng, X."Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15". Molecular Medicine Reports 31.5 (2025): 122.
Chicago
Huang, M., Chang, J., Liu, Y., Yin, J., Zeng, X."Apelin/APJ alleviates diabetic nephropathy by improving glomerular endothelial cells dysfunction via SIRT3‑KLF15". Molecular Medicine Reports 31, no. 5 (2025): 122. https://doi.org/10.3892/mmr.2025.13487
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