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Sci Rep. 2016 May 17;6:26072. doi: 10.1038/srep26072.

MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ, and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy.

Wu L1,2, Wang Q1, Guo F1, Ma X1, Ji H1,2, Liu F1, Zhao Y1, Qin G1.

Author information

1
Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
2
Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Abstract

MicroRNAs play important roles in the pathogenesis of diabetic nephropathy (DN). In this study, we found that high glucose upregulated miR-27a expression in cultured glomerular mesangial cells and in the kidney glomeruli of streptozotocin (STZ)-induced diabetic rats. miR-27a knockdown prevented high glucose-induced mesangial cell proliferation and also blocked the upregulation of extracellular matrix (ECM)-associated profibrotic genes. Reduction of cell proliferation and profibrotic gene expression by a miR-27a inhibitor depended upon the expression of peroxisome proliferator-activated receptor γ (PPARγ). Further studies showed that miR-27a negatively regulated PPARγ expression by binding to the 3'-untranslated region of rat PPARγ. An antisense oligonucleotide specific to miR-27a (antagomir-27a) significantly reduced renal miR-27a expression in STZ-induced diabetic rats and significantly increased PPARγ levels. Antagomir-27a also reduced kidney ECM accumulation and proteinuria in STZ-induced diabetic rats. These findings suggest that specific reduction of renal miR-27a decreases renal fibrosis, which may be explained in part by its regulation of PPARγ, and that targeting miR-27a may represent a novel therapeutic approach for DN.

PMID:
27184517
PMCID:
PMC4869109
DOI:
10.1038/srep26072
[Indexed for MEDLINE]
Free PMC Article

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