2021 Fiscal Year Final Research Report
Cytoglobin overexpression inhibits liver fibrosis and cancer development via anti-oxidant function
| Project/Area Number |
19K08428
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Liver fibrosis / Hepatic stellate cells / Cytoglobin / Antioxidant |
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| Outline of Final Research Achievements |
We have investigated the role of endogenous CYGB on liver diseases using CYGB deficient (Cygb-KO) mice and CYGB transgenic (Cygb-TG) mice under 10 weeks after thioacetamide (TAA) injection, or 16 weeks of choline deficient amino acid define diet (CDAA) feeding. These all models showed that absence of Cygb significantly exacerbated liver damage, fibrosis and reactive oxygen species (ROS) formation which were attenuated in Cygb-overexpressing mice. We have produced 6His-tagged recombinant human CYGB (His-CYGB). In cultured HSCs, His-CYGB was endocytosed and accumulated in endosomes via clathrin-mediated pathway. His-CYGB significantly impeded ROS formation spontaneously or in the presence of ROS inducers in HSCs, thus leading to the attenuation of collagen type I alpha 1 production and alpha-smooth muscle actin expression. Intravenously injected His-CYGB markedly suppressed liver inflammation, fibrosis and oxidative cell damage in TAA- or DDC-administered mice without adverse effects.
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| Free Research Field |
Hepatology
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| Academic Significance and Societal Importance of the Research Achievements |
抗線維化療法は、ヒトの慢性肝疾患において満たされていない医学的ニーズのままです。 現在、線維症の理解に大きな進歩があり、肝線維形成の根底にある複数のメカニズムが明らかにされていますが、特定の効果的な抗線維化療法はとらえどころのないままです。 損傷後の肝臓の修復は高度に調整された調整されたプロセスであり、線維症を抑制することで肝臓を健康な状態に戻すことができます。 価値のある治療法を見つけるためのこれらの取り組みにおいて、肝硬変および癌の発症におけるCYGBの保護的役割は有望なものとなる可能性があります。
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