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MiR-29b modulates DNA methylation in promoter region of miR-130b in mouse model of Diabetic nephropathy

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Abstract

Epigenetic modifications play a role in Diabetic Nephropathy (DN). Downregulation of miR-29b leads to modulation of DNA methylation via DNA methyl transferases (DNMTs) and hence exaggerated renal fibrosis in DN. Therefore, the main aim of the study was to evaluate effect of miR-29b expression in vivo on DNMTs, renal fibrosis, glomerular and tubular damage as well as renal morphology in DN. In order to explore the role of miR-29b in DNA methylation of other miRNAs, methylation profiling study was performed. It revealed that miR-29b was involved in methylation on of miR-130b on the cytosine guanine dinucleotides rich DNA (CpG) island 1 located on promoter region. In conclusion, miR-29b expression was found to modulate DNA methylation via DNMTs and regulate methylation of miR-130b. The result of this study provides a future direction to unveil role of miRNA expression in DNA methylation and its consequent effect on other miRNAs in DN.

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References

  1. Kharroubi AT, Darwish HM. Diabetes mellitus: The epidemic of the century. World J Diabetes. 2015;6(6):850–67.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cho NH, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.

    Article  CAS  PubMed  Google Scholar 

  3. Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. Am J Kidney Dis. 2018;71(6):884–95.

    Article  PubMed  Google Scholar 

  4. Reddy MA, Park J Tak, Natarajan R. Epigenetic modifications in the pathogenesis of diabetic nephropathy. Semin Nephrol. 2013; 33(4):341–53.

  5. Keating ST, et al. Epigenetics in diabetic nephropathy, immunity and metabolism. Diabetologia. 2018;61(1):6–20.

    Article  CAS  PubMed  Google Scholar 

  6. Morgado-Pascual JL, et al. Epigenetic Modification Mechanisms Involved in Inflammation and Fibrosis in Renal Pathology. Mediators Inflamm. 2018;2018:14.

    Article  Google Scholar 

  7. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402.

  8. Wang L-P, et al. MicroRNAs in the Progress of Diabetic Nephropathy: A Systematic Review and Meta-Analysis. Evid-Based Complement Altern Med. 2019;2019:9.

    Google Scholar 

  9. Lu Z, Liu N, Wang F. Epigenetic Regulations in Diabetic Nephropathy. J Diabetes Res. 2017;2017:6.

    Article  Google Scholar 

  10. Liu R, Lee K, He JC. Genetics and Epigenetics of Diabetic Nephropathy. Kidney Dis. 2015;1(1):42–51.

    Article  Google Scholar 

  11. Kavya J, Piyush G, Prathibha K, Bhagyashri K, Aditya S, Kiran K. Cognitive dysfunction: a growing link between diabetes and Alzheimer’s disease. Drug Dev Res. 2020;81(2):144–-64.

  12. Bansal A, Pinney SE. DNA methylation and its role in the pathogenesis of diabetes. Pediatr Diabetes. 2017;18(3):167–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gondaliya P, et al. miR29b regulates aberrant methylation in In-Vitro diabetic nephropathy model of renal proximal tubular cells. PLoS One. 2018;13(11):e0208044.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang G, et al. DNA methyltransferase 3, a target of microRNA-29c, contributes to neuronal proliferation by regulating the expression of brain-derived neurotrophic factor. Mol Med Rep. 2015;12(1):1435–42.

    Article  CAS  PubMed  Google Scholar 

  15. Guo J, et al. MiRNA-29c regulates the expression of inflammatory cytokines in diabetic nephropathy by targeting tristetraprolin. Sci Rep. 2017;7(1):2314.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Conserva F, et al. Urinary miRNA-27b-3p and miRNA-1228-3p correlate with the progression of Kidney Fibrosis in Diabetic Nephropathy. Sci Rep. 2019;9(1):11357.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Smyth LJ, et al. Validation of differentially methylated microRNAs identified from an epigenome-wide association study; Sanger and next generation sequencing approaches. BMC Res Notes. 2018;11(1):767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Srivastava SP, Koya D, Kanasaki K. MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT. Biomed Res Int. 2013;2013:125469

  19. Petrillo F, et al. MicroRNAs in Renal Diseases: A Potential Novel Therapeutic Target. Kidney Dis. 2017;3(3):111–9.

    Article  Google Scholar 

  20. Chen H-Y, et al. MicroRNA-29b inhibits diabetic nephropathy in db/db mice. Mol Ther. 2014;22(4):842–53.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97.

    Article  CAS  PubMed  Google Scholar 

  22. Lu Z, Liu N, Wang F. Epigenetic Regulations in Diabetic Nephropathy. J Diabetes Res. 2017;2017:7805058–7805058.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Singh K, et al. Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy. Mol Ther. 2017;25(12):2689–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sankrityayan H, Kulkarni YA, Gaikwad AB. Diabetic nephropathy: The regulatory interplay between epigenetics and microRNAs. Pharmacol Res. 2019;141:574–85.

    Article  CAS  PubMed  Google Scholar 

  25. Bai X, et al. MicroRNA-130b improves renal tubulointerstitial fibrosis via repression of Snail-induced epithelial-mesenchymal transition in diabetic nephropathy. Sci Rep. 2016;6:20475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gondaliya P, P. Dasare A, Jash K, Tekade RK, Srivastava A, Kalia K. miR-29b attenuates histone deacetylase-4 mediated podocyte dysfunction and renal fibrosis in diabetic nephropathy. J Diabetes Metab Disord. 2020;19:13–27.

  27. Sun T, et al. Down-regulated miR-15a mediates the epithelial–mesenchymal transition in renal tubular epithelial cells promoted by high glucose. Biosci Biotechnol Biochem. 2014;78(8):1363–70.

    Article  CAS  PubMed  Google Scholar 

  28. Wang B, et al. Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 2012;23(2):252–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhao Y, et al. MiR-30c protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition in db/db mice. Aging Cell. 2017;16(2):387–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jiang L, et al. A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-β1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis. Kidney Int. 2013;84(2):285–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang B, et al. miR-200a prevents renal fibrogenesis through repression of TGF-β2 expression. Diabetes. 2011;60(1):280–287.

  32. Zhang L, Zhang Q, Liu S, Chen Y, Li R, Lin T, Yu C, Zhang H, Huang Z, Zhao X, Tan XDNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury. Kidney Int. 2017;92(1):140–53.

  33. Larkin BP, et al. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease. FASEB J. 2018;32(10):5215–26.

    Article  CAS  PubMed  Google Scholar 

  34. Satirapoj B. Tubulointerstitial Biomarkers for Diabetic Nephropathy. J Diabetes Res. 2018;2018:2852398–2852398.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Qin W, et al. TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29. J Am Soc Nephrol. 2011;22(8):1462–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sugimoto H, et al. Renal Fibrosis and Glomerulosclerosis in a New Mouse Model of Diabetic Nephropathy and Its Regression by Bone Morphogenic Protein-7 and Advanced Glycation End Product Inhibitors. Diabetes. 2007;56(7):1825–33.

    Article  CAS  PubMed  Google Scholar 

  37. Kaimori J-Y, et al. Visualization of kidney fibrosis in diabetic nephropathy by long diffusion tensor imaging MRI with spin-echo sequence. Sci Rep. 2017;7(1):5731.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Putta S, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol. 2012;23(3):458–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Willmer T, et al. Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications. Front Endocrinol. 2018;9:744–744.

    Article  Google Scholar 

  40. Zuo T, et al. Methods in DNA methylation profiling. Epigenomics. 2009;1(2):331–45.

    Article  CAS  PubMed  Google Scholar 

  41. Yong W-S, Hsu F-M, Chen P-Y. Profiling genome-wide DNA methylation. Epigenetics Chromatin. 2016;9(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sun T, et al. Down-regulated miR-15a mediates the epithelial-mesenchymal transition in renal tubular epithelial cells promoted by high glucose. Biosci Biotechnol Biochem. 2014;78(8):1363–70.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The research was carried out at National Institute of Pharmaceutical Education and Research- Ahmedabad with the financial aid from the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India.

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Contributions

Conceptualization, Formal analysis and Methodology was done by Piyush Gondaliya. Data curation, Investigation and Writing – original draft was performed by Piyush Gondaliya and Kavya Jash. Supervision, and Writing – review & editing was done by Akshay Srivastava. Conceptualization, Project administration, Resources and Supervision was performed by Kiran Kalia. All authors read and approved the final manuscript.

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Correspondence to Kiran Kalia.

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All applicable institutional guidelines for the care and use of animals were followed. All procedures performed in this study involving animals were in accordance with the ethical standards of the institution at which the study was conducted (NIPER-A institutional animal ethics committee, NIPER-A/IAEC/2017/032).

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The authors declare that they have no conflict of interest.

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Gondaliya, P., Jash, K., Srivastava, A. et al. MiR-29b modulates DNA methylation in promoter region of miR-130b in mouse model of Diabetic nephropathy. J Diabetes Metab Disord 22, 1105–1115 (2023). https://doi.org/10.1007/s40200-023-01208-2

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