Didymin Alleviates Hepatic Fibrosis Through Inhibiting ERK and PI3K/Akt Pathways via Regulation of Raf Kinase Inhibitor Protein

被引：64

作者：

Lin, Xing ^{[1
]}

Bai, Faicheng ^{[1
]}

Nie, Jinlan ^{[1
]}

Lu, Shengjuan ^{[1
]}

Lu, Chunyuang ^{[1
]}

Zhu, Xunshuai ^{[1
]}

Wei, Jinbin ^{[1
]}

Lu, Zhongpeng ^{[2
]}

Huang, Quanfang ^{[2
]}

机构：

[1] Guangxi Med Univ, Nanning, Peoples R China

[2] Guangxi Univ Chinese Med, Affiliated Hosp 1, Nanning 530023, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2016年 / 40卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Didymin; Mitochondrial dysfunction; ERK/MAPK pathway; PI3K/Alct pathway; RKIP; CELL-PROLIFERATION; APOPTOTIC PATHWAY; MIGRATION; RKIP;

D O I：

10.1159/000453194

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Didymin has been reported to have anti-cancer potential. However, the effect of didymin on liver fibrosis remains illdefined. Methods: Hepatic fibrosis was induced by CCI4 in rats. The effects of didymin on liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminases activities and collagen-related indicators levels were determined by commercially available kits. Moreover, the effects of didymin on hepatic stellate cell apoptosis and cell cycle were analyzed by flow cytometry. Mitochondrial membrane potential was detected by using rhodamine-123 dye. The expression of Raf kinase inhibitor protein (RKIP) and the phosphorylation of the ERK/MARK and PI3K/Akt pathways were assessed by Western blot. Results: Didymin significantly ameliorated chronic liver injury and collagen deposition. It strongly inhibited hepatic stellate cells proliferation, induced apoptosis and caused cell cycle arrest in G2/M phase. Moreover, didymin notably attenuated mitochondria' membrane potential, accompanied by release of cytochrome C. Didymin significantly inhibited the ERK/MAPK and PI3K/Alct pathways. The effects of didymin on the collagen accumulation in rats and on the biological behaviors of hepatic stellate cells were largely abolished by the specific RKIP inhibitor locostatin. Conclusion: Didymin alleviates hepatic fibrosis by inhibiting ERK/MAPK and PI3K/Akt pathways via regulation of RKIP expression. (C) 2016 The Author(s) Published by S. Karger AG, Basel

引用

页码：1422 / 1432

页数：11

共 28 条

[1] Liver fibrosis [J].