Title: miRNA101a, functioning as an endogenous TGF-β signaling inhibitor, regulates cardiac fibrosis and remodeling through the regulation of Apoptosis and Autophagy

Biography:

Peipei Wang is a Research Assistant Professor at Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and Cardiac Department, National University Health System.

Abstract

Epigenetics, including DNA methylation, histone methylation and non-coding RNA, plays a very important role in cardiovascular diseases. In this talk I will introduce the therapeutic potentials of miRNA-101a mimics in the treatment of sustained hypertension-induced cardiac fibrosis and remodeling. Our work demonstrated that miR-101a and TGF-β1 mutually inhibits each other from studies of ex vivo cultured primary cardiac fibroblasts (cFBs) and in vivo transverse aortic constriction (TAC) model. miR-101a functions as an endogenous TGF-β1 signaling inhibitor and escape from miR-101a inhibition may lead to the development of fibrosis. Our novel findings include: (1) miR-101a inhibits cFB proliferation through promoted apoptosis; activation by down-regulation expression of α-SMA and fibronectin with EDA; collagen synthesis and secretion through enhance of autophagy, (2) TGF-β1 reduces miR-101a expression through inhibition of miR-101a promoter activity. Meanwhile miR-101a inhibits TGF-β1 signaling pathway but does not affect TGF-β1 expression and (3) we further tested the efficacy of miRNA-101a treatment in a TAC model. Our data demonstrate that early treatment of miR-101a mimics could supplement the loss of miR-101a, inhibit the activation of TGF-β signaling pathway, therefore reduce cardiac fibrosis and improve cardiac function.