Current Medical Science

, Volume 38, Issue 5, pp 758–764 | Cite as

Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway

  • Dong-wei Cao
  • Chun-ming Jiang
  • Cheng Wan
  • Miao Zhang
  • Qing-yan Zhang
  • Min Zhao
  • Bo Yang
  • Da-long Zhu
  • Xiao Han


Diabetic kidney disease (DKD) is a microvascular complication of type 2 diabetes. The study of DKD mechanisms is the most important target for the prevention of DKD. Renal senescence is one of the important pathogeneses for DKD, but the mechanism of renal and cellular senescence is unclear. Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD. This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs) induced by high glucose. HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640) in vitro. The effect of high glucose on morphology of HGMCs was observed 72 h after intervention. The cell cycle was examined by flow cytometry. The telomere length was measured by Southern blotting. The expression levels of p53, p21 and Rb proteins in p53-p21-Rb signaling pathway and p-stat1, p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively. The expression of miR-126 was examined by qRT-PCR. MiR-126 mimics was transfected into HGMCs. The effects of miR-126 mimics transfection on cell morphology, cell cycle, telomere length, p53, p21, Rb, p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1 phase but also shortened the telomere length. High glucose led to high expression of p53, p21, Rb, p-stat1 and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways. Moreover, the miR-126 was decreased in HGMCs induced by high glucose. It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs. The results may serve as a new strategy for the treatment of DKD.

Key words

diabetic kidney disease miR-126 human glomerular mesangial cells senescence telomere-p53-p21-Rb signaling pathway 


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  1. 1.
    Verzola D, Gandolfo MT, Gaetani G. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am J Physiol, 2008,295(5):1563–1573Google Scholar
  2. 2.
    Joyeeta B, Keichiro M, Deborshi B, et al. Telomere length as a potential biomarker of coronary artery disease. Indian J Med Res, 2017,145(6):730–737CrossRefGoogle Scholar
  3. 3.
    Feng C, Liu H, Yang M, et al. Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways. Cell Cycle, 2016,15(13):1674–1678CrossRefGoogle Scholar
  4. 4.
    Yang X, Liu S, Huang C, et al. Ochratoxin A induced premature senescence in human renal proximal tubular cells. Toxicology, 2017,382:75–83CrossRefGoogle Scholar
  5. 5.
    Boon RA, Iekushi K, Lechner S, et al. MicroRNA-34a regulates cardiac ageing and function. Nature, 2013,495(7439):107–110CrossRefGoogle Scholar
  6. 6.
    Olivieri F, Bonafè M, Spazzafumo L, et al. Ageand glycemia-related miR-126-3p levels in plasma and endothelial cells. Aging (Albany NY), 2014, 6(9):771–787CrossRefGoogle Scholar
  7. 7.
    Fiedler J, Grönniger E, Pfanne A, et al. Identification of miR-126 as a new regulator of skin ageing. Exp Dermatol, 2017,26(3):284–286CrossRefGoogle Scholar
  8. 8.
    Liu Y, Gao GQ, Yang C, et al. Stability of miR-126 in urine and its potential as a biomarker for renal endothelial injury with diabetic nephropathy. Int J Endocrinol, 2014,2014:393109Google Scholar
  9. 9.
    Al-Kafaji G, Al-Mahroos G, Al-Muhtaresh HA, et al. Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: A potential blood-based biomarker. Exp Ther Med, 2016,12(2):815–822CrossRefGoogle Scholar
  10. 10.
    Jiang R, Zhang C, Liu G, et al. MicroRNA-126 inhibits proliferation, migration, invasion, and EMT in osteosarcoma by targeting ZEB1. J Cell Biochem, 2017,118(11):3765–3774CrossRefGoogle Scholar
  11. 11.
    Marepally S, Boakye CH, Patel AR, et al. Topical administration of dual siRNAs using fusogenic lipid nanoparticles for treating psoriatic-like plaques. Nanomedicine (Lond), 2014,9(14):2157–2174CrossRefGoogle Scholar
  12. 12.
    Wang X, Lian Y, Wen X, et al. Expression of miR-126 and its potential function in coronary artery disease. Afr Health Sci, 2017,17(2):474–480CrossRefGoogle Scholar
  13. 13.
    Cao DW, Zhang M, Jiang CM, et al. Protection of Tanshinone IIA to human peritoneal mesothelial cells (HPMC) through delaying cellular senescence induced by high glucose. Ren Fail, 2012,34(1):88–94CrossRefGoogle Scholar
  14. 14.
    Wu Y, Cui W, Zhang D, et al. The shortening of leukocyte telomere length relates to DNA hypermethylation of LINE-1 in type 2 diabetes mellitus. Oncotarget, 2017,8(43):73 964–73 973Google Scholar
  15. 15.
    Feng X, Gao W, Li Y. Caveolin-1 is involved in high glucose accelerated human glomerular mesangial cell senescence. Korean J Intern Med, 2017,32(5):883–889CrossRefGoogle Scholar
  16. 16.
    Chen K, Dai H, Yuan J, et al. Optineurin-mediated mitophagy protects renal tubular epithelial cells against accelerated senescence in diabetic nephropathy. Cell Death Dis, 2018,9(2):105CrossRefGoogle Scholar
  17. 17.
    Liu R, Zhong Y, Li X, et al. Role of transcription factor acetylation in diabetic kidney disease. Diabetes, 2014,63(7):2440–2453CrossRefGoogle Scholar
  18. 18.
    Nakatani Y, Inagi R. Epigenetic regulation through SIRT1 in podocytes. Curr Hypertens Rev, 2016,12(2):89–94CrossRefGoogle Scholar
  19. 19.
    Aboulhoda BE. Age-related remodeling of the JAK/ STAT/SOCS signaling pathway and associated myocardial changes: From histological to molecular level. Ann Anat, 2017,214:21–30CrossRefGoogle Scholar
  20. 20.
    Huang JS, Lee YH, Chuang LY, et al. Cinnamaldehyde and nitric oxide attenuate advanced glycation end products-induced Jak/STAT signaling in human renal tubular cells. J Cell Biochem, 2015,116(6):1028–1038CrossRefGoogle Scholar
  21. 21.
    Yang M, Tian M, Zhang X, et al. Role of the JAK2/ STAT3 signaling pathway in the pathogenesis of type 2 diabetes mellitus with macrovascular complications. Oncotarget, 2017,8(57):96 958–96 969Google Scholar
  22. 22.
    Zhang X, Song S, Luo H. Regulation of podocyte lesions in diabetic nephropathy via miR-34a in the Notch signaling pathway. Medicine (Baltimore), 2016,95(44):e5050CrossRefGoogle Scholar
  23. 23.
    Liu H, French BA, Li J, et al. Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice. Exp Mol Pathol, 2015,99(3):552–557CrossRefGoogle Scholar
  24. 24.
    Meng S, Cao JT, Zhang B, et al. Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol, 2012,53(1):64–72CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2018

Authors and Affiliations

  • Dong-wei Cao
    • 1
    • 2
  • Chun-ming Jiang
    • 1
    • 2
  • Cheng Wan
    • 2
  • Miao Zhang
    • 2
  • Qing-yan Zhang
    • 2
  • Min Zhao
    • 2
  • Bo Yang
    • 3
  • Da-long Zhu
    • 4
  • Xiao Han
    • 5
  1. 1.Department of Nephrology, Nanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjingChina
  2. 2.Department of Nephrology, Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
  3. 3.Department of Dermatology, Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  4. 4.Department of Endocrinology, Nanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjingChina
  5. 5.Basic Medical SchoolNanjing Medical UniversityNanjingChina

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