| 研究実績の概要 |
The role of Cygb in anti-fibrosis and cancer were examined in different models of liver injuries including chemical induced liver fibrosis using thioacetamide (TAA) treatment for 10 weeks; diet induced non-alcoholic fatty liver diseases (NASH) using choline deficient amino acid define (CDAA) diet for 16 weeks, and bile duct ligation (BDL) for 24-72h and 1-3 weeks. We found that in the absence of Cygb liver injuries were magnified in Cygb-KO mice. In contrast, Cygb overexpression protected mice from liver damage induced by different etiologies. Microarray analysis from 1 week of BDL in all WT, KO, TG livers indicated CYGB regulated oxidative stress pathway including Nox-1, antioxidant protein 1, N-acetyltransferase 8, and myeloperoxidase is responsible for BDL-induced liver fibrosis. In TAA model, TG mice significantly ameliorated liver inflammation and fibrosis compared to WT ones. Furthermore, we produced rhCYGB protein and found that rhCYGB possess antioxidant and peroxidase activities.For in vitro experiments, we use hepatic stellate cells HHSteC cell line which show the most relevant to primary human HSCs. His-CYGB treated human hepatic stellate cells HHSteC showed time and dose dependently decreased αSMA and collagen expression at both protein and mRNA levels. In vivo model, rhCYGB administration in TAA-treated mice inhibited liver injuries, inflammation and fibrosis development.These results indicated that rhCYGB may inhibit HSCs activation and suppress fibrosis development in vitro.
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