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
The Key Laboratory of Major Autoimmune Diseases, Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China; The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China.
The Key Laboratory of Major Autoimmune Diseases, Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China; The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China.
Toxicol Lett. 2018 Jun 1;289:86-98. doi: 10.1016/j.toxlet.2018.03.010. Epub 2018 Mar 10.
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.
SUMO化和去SUMO化是一个动态过程，已被证明与多种纤维化疾病有关。在此，我们发现去SUMO化蛋白酶家族成员之一的SENP2在CCl诱导的小鼠肝纤维化组织、原代肝星状细胞（HSCs）中表达降低，且在自发恢复后恢复。此外，用TGF-β1处理HSC-T6细胞导致SENP2显著减少。SENP2的异位表达阻碍了TGF-β1诱导的细胞活化和增殖，而敲低SENP2则显示出相反的效果。重要的是，SENP2促进了由TGF-β1激活的HSC-T6细胞的凋亡。此外，在用成脂分化混合物（MDI）处理后，在失活的HSCs中观察到SENP2的恢复。SENP2不足抑制了HSC-T6细胞的逆转，其特征是肝纤维化的两个标志物α-SMA和col1a1的异常表达。据报道，SENP2是Wnt/β-连环蛋白信号通路的抑制调节因子。同样，我们发现在肝纤维化中，SENP2对β-连环蛋白及其下游基因C-myc和CyclinD1也有负面影响。总的来说，我们的数据表明SENP2可能参与了肝纤维化中肝星状细胞的凋亡和逆转。
