文献类型：期刊文献

英文题名：Gant61 ameliorates CCl4-induced liver fibrosis by inhibition of Hedgehog signaling activity

作者：Shen Jiayuan[1,2];Yan Junyan[1];Wei Xiangzhen[3];Liu Zuping[1,2];Ni Jian[1];Hu Baowei[1];Jin Lifang[1]

机构：[1]Shaoxing Univ, Coll Life Sci, Shaoxing 312000, Zhejiang, Peoples R China;[2]Shaoxing Univ, Affiliated Hosp, Dept Pathol, Shaoxing, Zhejiang, Peoples R China;[3]Xian Jiaotong Liverpool Univ, Suzhou, Peoples R China

年份：2020

卷号：387

外文期刊名：TOXICOLOGY AND APPLIED PHARMACOLOGY

收录：SCI-EXPANDED(收录号：WOS:000512216800005)、、WOS

基金：This work was supported by research grants from Zhejiang Province Science and Technology Project of China (No. 2018C37105) and Scientific Research Platform of Molecular Pathology Detection Center for Tumor Genes, Shaoxing University. This work was also supported by the scientific research start-up funding of Shaoxing University (Grant No. 20185009).

语种：英文

外文关键词：Hedgehog signaling; Liver fibrosis; Gant61; Glis; Hepatic stellate cells

外文摘要：As an intercellular signaling molecule, Hedgehog (Hh) plays a critical role in liver fibrosis/regeneration. Transcription effectors Gli1 and Gli2 are key components of the Hh signaling pathway. However, whether inhibition of Gli1/2 activity can affect liver fibrogenesis is largely unknown. In the present study, we investigated the effect of Gant61 (a Gli1/2 transcription factor inhibitor) on liver fibrosis and its possible mechanism. Wildtype and Shh-EGFP-Cre male mice were exposed to CCl4, and then treated with or without Gant61 for four weeks. The level of liver injury/fibrosis and expression levels of mRNA and protein related to the Hh ligand/pathway were assessed. In our study, CCl4 treatment induced liver injury/fibrosis and promoted activation of hepatic stellate cells (HSCs). In addition, CCl4 induced the expression of Shh ligands in and around the fibrotic lesion, accompanied by induction of mRNA and protein expression of Hh components (Smo, Gli1 and Gli2). However, administration of Gant61 decreased liver fibrosis by reduction in HSC number, down-regulation of mRNA and protein expression of Hh components (Smo, Gli1 and Gli2), and cell-cycle arrest of HSCs. Our data highlight the importance of the Shh pathway for the development of liver fibrosis, and also suggest Glis as potential therapeutic targets for the treatment of liver fibrosis.