MiR-101a ameliorates AngII-mediated hypertensive nephropathy by blockade of TGFβ/Smad3 and NF-κB signaling in a mouse model of hypertension.

Hypertensive nephropathy, clinically characterized by progressive renal fibrosis and inflammation, is a severe complication of hypertension. The objectives of this study were to investigate the roles of miR-101a in relieving Angiotensin II (Ang II)-mediated hypertensive nephropathy and uncover the possible underlying mechanisms. Hypertensive mouse model was established via continuous 28-day AngII infusion. Systolic blood pressure (SBP), ratio of urine albumin to creatinine, blood urea nitrogen (BUN), serum creatinine (Scr) and glomerular filtration rate (GFR) were evaluated. Dual luciferase reporter assay was used to explore the target of miR-101a. mRNA levels of miR-101a, TGFβRI, fibrotic markers (Collagen I and α-SMA) and pro-inflammatory cytokines (IL-1β and TNF-α) were determined by real-time PCR. Protein levels of TGFβRI, Collagen I, α-SMA, IL-1β, TNF-α, t-p65, P-p65, t-Smad3, P-Smad3, t-IκBα and P-IκBα were detected by Western blot. MiR-101a mimics significantly improved GFR and inhibited AngII-induced increase in the ratio of urine albumin to creatinine, BUN and Scr. MiR-101a mimics partially abolished AngII-induced increase in the mRNA and protein level of fibrotic markers by targeting TGFβRI and inhibiting TGFβ/Smad3 pathway. Moreover, TGFβRI inhibitor galunisertib inhibited AngII-mediated renal injury in mice with hypertensive nephropathy. Additionally, miR-101a overexpression blocked AngII-induced up-regulation of pro-inflammatory markers via suppressing NF-κB pathway. MiR-101a exhibited protective effects against hypertensive nephropathy via inhibiting TGFβ/Smad3 and NF-κB signaling pathways. This article is protected by copyright. All rights reserved.