title: Effect of miR-21 on renal fibrosis by regulating MMP-9 and TIMP1 in kk-ay diabetic nephropathy mice.
abstract: 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.
authors: School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.
authors: Jinyang
authors: J
authors: Wang
authors: Yanbin
authors: Y
authors: Gao
authors: Mingfei
authors: M
authors: Ma
authors: Minzhou
authors: M
authors: Li
authors: Dawei
authors: D
authors: Zou
authors: Jinkui
authors: J
authors: Yang
authors: Zhiyao
authors: Z
authors: Zhu
authors: Xuan
authors: X
authors: Zhao
mesh_terms: D000419:Albuminuria / Q000150:complications; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D003401:Creatine / Q000652:urine; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000652:urine; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; D005353:Fibronectins; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D003401:Creatine