文献类型：期刊文献

英文题名：Shh-Yapsignaling controls hepatic ductular reactions inCCl(4)-induced liver injury

作者：Jin, Lifang[1];Huang, Huarong[2];Ni, Jian[1];Shen, Jiayuan[3];Liu, Zuping[3];Li, Lijing[1];Fu, Shengmin[1];Yan, Junyan[1];Hu, Baowei[1]

机构：[1]Shaoxing Univ, Sch Life Sci, Shaoxing 312000, Zhejiang, Peoples R China;[2]Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Peoples R China;[3]Shaoxing Univ, Affiliated Hosp, Dept Pathol, Shaoxing, Zhejiang, Peoples R China

年份：2021

卷号：36

期号：2

起止页码：194

外文期刊名：ENVIRONMENTAL TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:000573653800001)、、EI(收录号：20204009291019)、Scopus(收录号：2-s2.0-85091729952)、WOS

基金：Shaoxing University, Grant/Award Number: 20185009; Scientific Research Platform of Molecular Pathology Detection Center for Tumor Genes, Shaoxing University; Zhejiang Province Science and Technology Project of China, Grant/Award Number: 2018C37105; Research Fund Program of National Natural Science Foundation of China, Grant/Award Number: 21876115

语种：英文

外文关键词：carbon tetrachloride; ductular reaction; Gant61; sonic hedgehog signaling; Yap1 signaling

外文摘要：Carbon tetrachloride (CCl4) exposure can induce hepatic ductular reactions. To date, however, the related mechanism remains largely unknown. Sonic hedgehog (Shh) and Yes-associated protein (Yap) signaling are correlated with liver injury and regeneration. Herein, we investigated the role of Shh and Yap signaling in the fate of ductular reaction cells in CCl4-treated livers and the possible mechanisms. Wild-type and Shh-EGFP-Cre male mice were exposed to CCl4(2 mL/kg), and then treated with or without the Shh signaling inhibitor Gant61. The level of liver injury, proliferation of ductular reaction cells, and expression levels of mRNA and protein related to the Shh and Yap signaling components were assessed. Results showed that CCl(4)treatment induced liver injury and promoted activation and proliferation of ductular reaction cells. In addition, CCl(4)induced the expression of Shh ligands in hepatocytes, accompanied by activation of Shh and Yap1 signaling in the liver. Furthermore, administration of Gant61 ameliorated liver regeneration, inhibited hepatic ductular reactions, and decreased Shh and Yap1 signaling activity. Thus, Shh-Yap1 signaling appears to play an integral role in the proliferation of ductular reaction cells in CCl4-induced liver injury. This study should improve our understanding of the mechanism of CCl4-induced liver injury and ductular reactions and provide support for future investigations on liver disease therapy.