Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling
| Autor: | Fei Li, Fang Liu, Qi Zhao, Jia-Peng Hu, Xue-Rong Xiao, Dandan Hu, Tao Jiang, Yan Cheng, Frank J. Gonzalez, Jin-Hui Yang, Ying-Mei Tang, Wei-Min Bao |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Receptors Cytoplasmic and Nuclear Cholestasis Intrahepatic Thioacetamide Pharmacology Biochemistry Analytical Chemistry Mice 03 medical and health sciences chemistry.chemical_compound Sirtuin 1 Cholestasis medicine Animals Humans Metabolomics Molecular Biology 030304 developmental biology Liver injury 0303 health sciences biology Chemistry Gene Expression Profiling Research 030302 biochemistry & molecular biology Middle Aged biology.organism_classification medicine.disease Triterpenes Disease Models Animal Treatment Outcome 1-Naphthylisothiocyanate Celastrol biology.protein Female Farnesoid X receptor Signal transduction Pentacyclic Triterpenes Tripterygium Signal Transduction |
| Zdroj: | Molecular & Cellular Proteomics. 18:520-533 |
| ISSN: | 1535-9476 |
| DOI: | 10.1074/mcp.ra118.000817 |
| Popis: | 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 α-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. |
| Databáze: | OpenAIRE |
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