Shanfei Ge1, Lunli Zhang1, Jianping Xie2, Fei Liu2, Jinni He3, Jinwen He3, Xiaowei Wang4, Tianxing Xiang1. 1. Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. 2. Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China. 3. Xiangya School of Medicine, Central South University, Changsha, Hunan, China. 4. BGI-tianjin, Tianjin, China.
Abstract
Background. We previously identified miR-146b as being up-regulated during the development of hepatic fibrosis using deep sequencing technology and gene expression analysis. However, the roles and related mechanisms of miR-146b in hepatic stellate cells (HSCs), which are involved in fibrogenesis and fibrosis, have not been elucidated. RESULTS: We report that miR-146b expression was increased in TGF-ß1-treated HSCs. TGF- ß1 enhanced α-SMA and COL1A1 protein expression in HSCs and stimulated proliferation of these cells compared with cells transfected with inhibitor NC. Conversely, miR-146b knock-down decreased α-SMA and COL1A1 expression and inhibited HSC proliferation. In addition, we found that miR-146b specifically regulated the translation of Krüppel-like factor 4 (KLF4) by targeting its 3' untranslated region. Forced expression of KLF4 inhibited TGF- ß1-induced enhancement of α-SMA and COL1A1 expression in HSCs, as well as proliferation of these cells. Moreover, miR-146b expression was negatively associated with KLF4 expression but positively associated with expression of α-SMA and COL1A1 during hepatic fibrosis. CONCLUSIONS: Our findings demonstrate the participation of miR-146b as a novel upstream effector of HSC activation via direct targeting of KLF4. Thus, targeted transfer of miR-146b into HSCs could be a useful strategy for the treatment of hepatic fibrosis.
Background. We previously identified miR-146b as being up-regulated during the development of hepatic fibrosis using deep sequencing technology and gene expression analysis. However, the roles and related mechanisms of miR-146b in hepatic stellate cells (HSCs), which are involved in fibrogenesis and fibrosis, have not been elucidated. RESULTS: We report that miR-146b expression was increased in TGF-ß1-treated HSCs. TGF- ß1 enhanced α-SMA and COL1A1 protein expression in HSCs and stimulated proliferation of these cells compared with cells transfected with inhibitor NC. Conversely, miR-146b knock-down decreased α-SMA and COL1A1 expression and inhibited HSC proliferation. In addition, we found that miR-146b specifically regulated the translation of Krüppel-like factor 4 (KLF4) by targeting its 3' untranslated region. Forced expression of KLF4 inhibited TGF- ß1-induced enhancement of α-SMA and COL1A1 expression in HSCs, as well as proliferation of these cells. Moreover, miR-146b expression was negatively associated with KLF4 expression but positively associated with expression of α-SMA and COL1A1 during hepatic fibrosis. CONCLUSIONS: Our findings demonstrate the participation of miR-146b as a novel upstream effector of HSC activation via direct targeting of KLF4. Thus, targeted transfer of miR-146b into HSCs could be a useful strategy for the treatment of hepatic fibrosis.
Authors: Hend A El-Taweel; Yasmine A Issa; Rasha F Mady; Ghada A Shehata; Eman A Youssef; Mona M Tolba Journal: Parasitol Res Date: 2022-05-16 Impact factor: 2.383
Authors: Liting Zhang; Jing Gao; Dan Zhou; Xiaojun Wang; Junfeng Li; Juan Wang; Hong Chen; Xiaodong Xie; Tuo Chen Journal: Ann Transl Med Date: 2021-09