Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice

• Published in: Cell biochemistry and biophysics Vol. 67; no. 2; pp. 537 - 546
• Main Authors: Wang, Jinyang, Gao, Yanbin, Ma, Mingfei, Li, Minzhou, Zou, Dawei, Yang, Jinkui, Zhu, Zhiyao, Zhao, Xuan
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.11.2013; Springer Nature B.V
• Subjects: Albuminuria - complications; Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Cell Biology; Collagen Type IV - metabolism; Creatine - urine; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - urine; Fibronectins - metabolism; Fibrosis - genetics; Fibrosis - metabolism; Gene Expression Regulation, Enzymologic; Kidney - pathology; Life Sciences; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Original Paper; Pharmacology/Toxicology; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; ACR; miRNA; Diabetic nephropathy; Ccr; MMP-9 and TIMP-1; ECM
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-013-9539-2

MicroRNAs (miRs) play important roles in initiation and progression of many pathologic processes. However, the roles of miRs in diabetic nephropathy remain unclear. This study was to determine whether miR-21 was involved in diabetic nephropathy and to explore the relationship between miR-21 and MMP9/TIMP1 expression in diabetic nephropathy. In situ hybridization studies showed that miR-21 was primarily localized and distributed in cortical glomerular and renal tubular cells in diabetic kk-ay kidney. Real-time quantitative RT-PCR demonstrated that the expression of miR-21 was significantly increased in kk-ay mice, compared with control C57BL mice. Interestingly, miR-21 expression positively correlated with urine albumin creatine ratio (ACR), TIMP1, collagen IV (ColIV), and fibronectin (FN); while negatively correlated with creatine clearance ratio (Ccr) and MMP-9 protein. Importantly, antagomir-21 not only ameliorated Ccr and ACR but also decreased TIMP1, ColIV, and FN proteins. In conclusion, our data demonstrate that miR-21 contributes to renal fibrosis by mediating MMP9/TIMP1 and that inhibition of miR-21 may be a novel target for diabetic nephropathy.