SENP2 alleviates CCl 4 -induced liver fibrosis by promoting activated hepatic stellate cell apoptosis and reversion

• Published in: Toxicology letters 2018-03
• Main Authors: Bu, Fang-Tian, Chen, Yu, Yu, Hai-Xia, Chen, Xin, Yang, Yang, Pan, Xue-Yin, Wang, Qin, Wu, Yu-Ting, Huang, Cheng, Meng, Xiao-Ming, Li, Jun
• Format: Article
• Language: English
• ISSN: 1879-3169

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 CCl -induced mice fibrotic liver tissues, primary HSCs and restored after spontaneously recovery. In addition, HSC-T6 cells with TGF-β1 treatment resulted in a significant reduction of SENP2. Ectopic expression of SENP2 hindered cells activation and proliferation induced by TGF-β1 while knockdown of SENP2 showed an opposite effect. Importantly, SENP2 promoted apoptosis of HSC-T6 cells activated by TGF-β1. 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 α-SMA and col1a1, two markers of liver fibrosis. It has been reported SENP2 was a suppressant regulator of Wnt/β-catenin signal pathway. Similarly, we found SENP2 has a negative effect on β-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.