| First Author | Wang B | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 1 | Pages | 280-7 |
| PubMed ID | 20952520 | Mgi Jnum | J:170163 |
| Mgi Id | MGI:4944098 | Doi | 10.2337/db10-0892 |
| Citation | Wang B, et al. (2011) miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes 60(1):280-7 |
| abstractText | OBJECTIVE: Progressive fibrosis in the diabetic kidney is driven and sustained by a diverse range of profibrotic factors. This study examines the critical role of microRNAs (miRNAs) in the regulation of the key fibrotic mediators, TGF-beta1 and TGF-beta2. RESEARCH DESIGN AND METHODS: Rat proximal-tubular epithelial cells (NRK52E) were treated with TGF-beta1 and TGF-beta2 for 3 days, and expression of markers of epithelial-to-mesenchymal transition (EMT) and fibrogenesis were assessed by RT-PCR and Western blotting. The expression of miR-141 and miR-200a was also assessed, as was their role as translational repressors of TGF-beta signaling. Finally, these pathways were explored in two different mouse models, representing early and advanced diabetic nephropathy. RESULTS: Both TGF-beta1 and TGF-beta2 induced EMT and fibrogenesis in NRK52E cells. TGF-beta1 and TGF-beta2 also downregulated expression of miR-200a. The importance of these changes was demonstrated by the finding that ectopic expression miR-200a downregulated smad-3 activity and the expression of matrix proteins and prevented TGF-beta-dependent EMT. miR-200a also downregulated the expression of TGF-beta2, via direct interaction with the 3' untranslated region of TGF-beta2. The renal expression of miR-141 and miR-200a was also reduced in mouse models representing early and advanced kidney disease. CONCLUSIONS: miR-200a and miR-141 significantly impact on the development and progression of TGF-beta-dependent EMT and fibrosis in vitro and in vivo. These miRNAs appear to be intricately involved in fibrogenesis, both as downstream mediators of TGF-beta signaling and as components of feedback regulation, and as such represent important new targets for the prevention of progressive kidney disease in the context of diabetes. |
