器官移植2025，Vol.16Issue(3)：425-434,10.DOI:10.12464/j.issn.1674-7445.2024278
MOTS-c通过调节转运体MRP2表达对甘氨鹅脱氧胆酸诱导的肝细胞损伤的影响
Effect of MOTS-c on hepatocyte injury induced by glycochenodeoxycholic acid by regulating transporter MRP2 expression
摘要
Abstract
Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid(GCDCA)-induced injury in human hepatocytes(THLE-3 cells).Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c.The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit(CCK)-8 method.Subsequently,THLE-3 cells were treated or pre-treated with GCDCA(200 µmol/L),MOTS-c(15,30,60 µmol/L),the multidrug resistance protein 2(MRP2)inhibitor Probenecid(500µmol/L),and the nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor ML385(10µmol/L).Cell proliferation was assessed by CCK-8 method.Lactate dehydrogenase(LDH)levels in the culture medium were measured by biochemical method.Cell apoptosis rates were determined by flow cytometry.MRP2 messenger RNA(mRNA)levels were detected by real-time quantitative polymerase chain reaction(RT-qPCR).MRP2 and Nrf2 protein expression levels were analyzed by Western blotting.Results As the concentration of GCDCA increased,the proliferation activity of THLE-3 cells gradually decreased,while LDH activity in the culture medium and apoptosis levels increased,and the expression levels of MRP2 in the cells decreased(all P<0.05).Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA,upregulated the expression of MRP2 and Nrf2,and reduced LDH activity and apoptosis levels(all P<0.05).Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury,while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA.Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes(THLE-3 cells),and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.关键词
胆汁淤积/缺血-再灌注损伤/肝移植/肝损伤/甘氨鹅脱氧胆酸/MOTS-c/核因子E2相关因子2/多药耐药蛋白2Key words
Cholestasis/Ischemia-reperfusion injury/Liver transplantation/Hepatocyte injury/Glycochenodeoxycholic acid/MOTS-c/Nuclear factor erythroid 2-related factor 2/Multidrug resistance protein 2分类
医药卫生引用本文复制引用
敖宇,张旭阳,唐聃,刘公伟,黄丹,蔡治方..MOTS-c通过调节转运体MRP2表达对甘氨鹅脱氧胆酸诱导的肝细胞损伤的影响[J].器官移植,2025,16(3):425-434,10.基金项目
贵州省卫生健康委科学技术基金项目(WJW-2021-014) （WJW-2021-014）
