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Background: 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.
Methods: In the present 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.
Results: 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-β1 axis in tubular epithelial cells undergoing EMT and thereby impeded the release of TGF- β1; oppositely, knockdown of miR-30c enhanced the secretion of TGF- β1 from epitheliums and significantly promoted proliferation of fibroblasts and fibrogenesis of myofibroblasts, aggravated tubulointerstitial fibrosis and dysfunction of diabetic nephropathy.
Conclusions: These results suggest a protective role of miR-30c against diabetic nephropathy by suppressing EMT via inhibiting Snail1-TGF- β1 pathway.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: MicroRNAs and Beyond in Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1127-355
- 2017 American College of Cardiology Foundation