Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation
نویسندگان
چکیده
Background and Purpose Liver fibrosis is one of the leading causes morbidity mortality worldwide but lacks any acceptable therapy. The transcription factor glioma-associated oncogene homologue 1 (GLI1) a potentially important therapeutic target in liver fibrosis. This study investigates anti-fibrotic activities potential mechanisms phytochemical, physalin B. Experimental Approach Two mouse models (CCl4 challenge bile duct ligation) were used to assess antifibrotic effects B vivo. Mouse primary hepatic stellate cells (pHSCs) human HSC line LX-2 also served as vitro models. fibrogenic genes, GLI1 downstream genes examined using Western blot quantitative real-time PCR (qRT-PCR). acetylation LAP2α–HDAC1 interaction analysed by co-immunoprecipitation. Key Results In vivo, administration attenuated histopathological injury collagen accumulation decreased expression genes. Physalin dose-dependently suppressed fibrotic marker pHSCs. Mechanistic studies showed that inhibited GLI activity non-canonical Hedgehog signalling. blocked formation lamina-associated polypeptide 2α (LAP2α)/histone deacetylase (HDAC1) complexes, thus inhibiting HDAC1-mediated deacetylation. up-regulated GLI1, down-regulated subsequently activation. Conclusion Implications exerted potent vivo disrupting LAP2α/HDAC1 increasing inactivating GLI1. indicates phytochemical may be candidate for treatment
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ژورنال
عنوان ژورنال: British Journal of Pharmacology
سال: 2021
ISSN: ['0007-1188', '1476-5381']
DOI: https://doi.org/10.1111/bph.15490