| First Author | Zhao Y | Year | 2017 |
| Journal | Aging Cell | Volume | 16 |
| Issue | 2 | Pages | 387-400 |
| PubMed ID | 28127848 | Mgi Jnum | J:240950 |
| Mgi Id | MGI:5896869 | Doi | 10.1111/acel.12563 |
| Citation | Zhao Y, et al. (2017) MiR-30c protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition in db/db mice. Aging Cell 16(2):387-400 |
| abstractText | Epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c. In vivo study showed that overexpression of miR-30c suppressed EMT, attenuated renal tubulointerstitial fibrosis and reduced proteinuria, serum creatinine, and BUN levels. In addition, Snail1 was identified as a direct target of miR-30c by Ago2 co-immunoprecipitation, luciferase reporter, and Western blot assays. Downregulating Snail1 by siRNA reduced high glucose-induced EMT in HK2 cells, and miR-30c mimicked the effects. Moreover, miR-30c inhibited Snail1-TGF-beta1 axis in tubular epithelial cells undergoing EMT and thereby impeded the release of TGF-beta1; oppositely, knockdown of miR-30c enhanced the secretion of TGF-beta1 from epitheliums and significantly promoted proliferation of fibroblasts and fibrogenesis of myofibroblasts, aggravated tubulointerstitial fibrosis, and dysfunction of diabetic nephropathy. These results suggest a protective role of miR-30c against diabetic nephropathy by suppressing EMT via inhibiting Snail1-TGF-beta1 pathway. |
