MicroRNA ‐145 induces the senescence of activated hepatic stellate cells through the activation of p53 pathway by ZEB2

In this study, we report that microRNA ‐145 (miR‐145) and p53 were downregulated in vivo and in vitro, concomitant with the enhanced expression of zinc finger E‐box binding homeobox 2 (ZEB2). In addition, overexpression of miR‐145 and p53 led to upregulation of the number of senescence‐associated β‐galactosidase‐positive H SCs and the expression of senescence markers p16 and p21, along with the reduced abundance of HSC activation markers α‐smooth muscle actin and type I collagen in activated HSCs. Furthermore, silencing of ZEB2 promoted senescence of activated HSCs. Moreover, we also demonstrated that miR‐145 spe cifically targeted the 3′‐untranslated regions of ZEB2. In vitro promoter regulation studies show that ZEB2 could bind to the E‐box of the p53 promoter as well as inhibit its promoter activity and thus suppress the expression of p53, which in turn repressed activated HSCs senescence. Taken tog ether, our results describe a novel miR‐145‐ZEB2‐p53 regulatory line might participate in the senescence of activated HSCs and might carry potential therapeutic targets for restraining liver fibrosis.

Source: Journal of Cellular Physiology - November 27, 2018 Category: Cytology Authors: Junfa Yang, Yuchen Lu, Peipei Yang, Qingfeng Chen, Yang Wang, Qi Ding, Tao Xu, Xiaofeng Li, Changyao Li, Cheng Huang, Xiaoming Meng, Jun Li, Lei Zhang, Xiao Wang Tags: ORIGINAL RESEARCH ARTICLE Source Type: research