| 研究実績の概要 |
We have examined therapeutic effects of 6-His tagged recombinant human Cytoglobin (rhCYGB) protein against mouse liver injuries/fibrosis and human HSC activation. We have completed investigating the role of endogenous CYGB on liver diseases using CYGB deficient (Cygb-KO) mice and CYGB transgenic (Cygb-TG) mice. We have completed 3 models of liver injuries using wild-type (WT), Cygb transgenic (TG), and knockout (KO) mice. Mice were sacrificed at 10 weeks after thioacetamide (TAA) injection, 16 weeks after choline deficient amino acid define diet (CDAA) feeding plus 4 weeks recovery or 12 months after diethylnitrosamine (DEN) treatment. These all three models showed that despite of different etiologies, absence of Cygb significantly exacerbated liver damage, fibrosis and reactive oxygen species (ROS) formation. All these manifestations were attenuated in Cygb-overexpressing mice. We have further produced 6His-tagged recombinant human CYGB (His-CYGB), traced its bio-distribution in vitro, and assessed its function in suppressing fibrosis synthesis in cultured human hepatic stellate cells (HHSteCs). We then compare the effect of full-length of rhCYGB protein and its shortening peptides. We found that the effect of rhCYGB in inhibiting Collagen synthesis in vitro can be kept with its core region from acid amine residue 18 to 180 in comparison with its full-length from 1-190 acid amine.
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