机构：[1]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China[2]University of Chinese Academy of Sciences, Beijing 100049, China[3]Department of Gastroenterology, The 2nd Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming 650033, China[4]Department of General Surgery, Yunnan Provincial 1st People’s Hospital, Kunming 650032, China[5]Clinical Laboratory, The 2nd Affiliated Hospital of Kunming Medical University, Kunming 650033, China[6]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892[7]State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, Jiangsu, China
Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by alpha-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.
基金：
National Key Research and Development Program of China [2017YFC1700906, 2017YFC0906903]; CAS "Light of West China" Program [Y72E8211W1]; Kunming Institute of Botany [Y76E1211K1, Y4662211K1]; State Key Laboratory of Phytochemistry and Plant Resources in West China [52Y67A9211Z1]; Open Fund of State Key Laboratory of Pharmaceutical Biotechnology, Nan-jing University [KF-GN-201705]
第一作者机构：[1]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China[2]University of Chinese Academy of Sciences, Beijing 100049, China
通讯作者：
通讯机构：[1]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China[3]Department of Gastroenterology, The 2nd Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming 650033, China[7]State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, Jiangsu, China[*1]Department of Gastroenterology, The 2nd Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming 650033, China.[*2]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
推荐引用方式(GB/T 7714)：
Zhao Qi,Liu Fang,Cheng Yan,et al.Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling[J].MOLECULAR & CELLULAR PROTEOMICS.2019,18(3):520-533.doi:10.1074/mcp.RA118.000817.
APA：
Zhao, Qi,Liu, Fang,Cheng, Yan,Xiao, Xue Rong,Hu, Dan Dan...&Li, Fei.(2019).Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling.MOLECULAR & CELLULAR PROTEOMICS,18,(3)
MLA：
Zhao, Qi,et al."Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling".MOLECULAR & CELLULAR PROTEOMICS 18..3(2019):520-533
