SENP2 alleviates CCl4-induced liver fibrosis by promoting activated hepatic stellate cell apoptosis and reversion

被引：24

作者：

Bu, Fang-Tian ^{[1
,2
,3
]}

Chen, Yu ^{[1
,2
,3
]}

Yu, Hai-Xia ^{[1
,2
,3
]}

Chen, Xin ^{[1
,2
,3
]}

Yang, Yang ^{[1
,2
,3
]}

Pan, Xue-Yin ^{[1
,2
,3
]}

Wang, Qin ^{[1
,2
,3
]}

Wu, Yu-Ting ^{[1
,2
,3
]}

Huang, Cheng ^{[1
,2
,3
]}

Meng, Xiao-Ming ^{[1
,2
,3
]}

Li, Jun ^{[1
,2
,3
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Anhui Inst Innovat Drugs, Key Lab Major Autoimmune Dis, Hefei, Anhui, Peoples R China

[2] Minist Educ, Key Lab Antiinflammatory Immune Med, Hefei, Anhui, Peoples R China

[3] Anhui Med Univ, Inst Liver Dis, Hefei, Anhui, Peoples R China

来源：

TOXICOLOGY LETTERS | 2018年 / 289卷

基金：

美国国家科学基金会;

关键词：

Liver fibrosis; SENP2; HSC; ss-catenin; HEPATOCELLULAR-CARCINOMA CELL; AXIN-BINDING PROTEIN; BETA-CATENIN; THERAPEUTIC TARGET; SUMO; SUMOYLATION; DESUMOYLATION; EXPRESSION; CANCER; REGRESSION;

D O I：

10.1016/j.toxlet.2018.03.010

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 [卫生毒理学];

摘要：

SUMOylation and deSUMOylation, a dynamic process, is proved to be involved in various fibrotic diseases. Here, we found SENP2, one of deSUMOylation protease family member, was decreased in CCl4-induced mice fibrotic liver tissues, primary HSCs and restored after spontaneously recovery. In addition, HSC-T6 cells with TGF-ss 1 treatment resulted in a significant reduction of SENP2. Ectopic expression of SENP2 hindered cells activation and proliferation induced by TGF-ss 1 while knockdown of SENP2 showed an opposite effect. Importantly, SENP2 promoted apoptosis of HSC-T6 cells activated by TGF-ss 1. Furthermore, restoration of SENP2 was observed in inactivated HSCs after adipogenic differentiation mixture (MDI) treatment. Inadequate SENP2 inhibited the reversion of HSC-T6 cells, featured as aberrant expressions of a-SMA and col1a1, two markers of liver fibrosis. It has been reported SENP2 was a suppressant regulator of Wnt/ss-catenin signal pathway. Similarly, we found SENP2 has a negative effect on ss-catenin as well as its downstream genes C-myc and CyclinD1 in liver fibrosis. Collectively, our data indicated SENP2 may be involved in HSCs apoptosis and reversion in liver fibrosis.

引用

页码：86 / 98

页数：13

共 43 条

[21]

Inhibition of sumoylation prevents experimental fibrosis [J].