2023 Fiscal Year Final Research Report
Treatment Strategy for liver fibrosis based on deactivation of fibrogenic hepatic stellate cells
| Project/Area Number |
21H02907
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柳川 享世 東海大学, 医学部, 助教 (10760291)
住吉 秀明 東海大学, 医学部, 准教授 (60343357)
紙谷 聡英 東海大学, 医学部, 准教授 (30321904)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 肝線維症 / 肝星細胞 / 脱活性化 |
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| Outline of Final Research Achievements |
Liver fibrosis is caused by activation of hepatic stellate cells (HSCs) that overproduce collagens and other ECM components. On the other hand, approximately a half of activated HSCs undergo deactivation after the cessation of fibrogenic stimuli, and their phenotype returns, at least in part, to that of quiescent HSCs. We recently reported Tcf21 as a novel deactivation factor of fibrogenic HSCs.
In the present study, we explored how deactivation of HSCs accelerates the repair of injured liver and regeneration of fibrotic liver from the viewpoint of crosstalk between deactivated HSCs and neighboring cells. For this purpose, we established a tracing mouse strain that allows specific and permanent labeling of activated HSCs, and identified several small molecules that mimic the anti-fibrotic effect of Tcf21.
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| Free Research Field |
肝臓病学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでの肝線維化研究では、星細胞の活性化や筋線維芽細胞への形質転換の阻害、あるいは活性型星細胞によるコラーゲン産生の抑制に基づく肝線維症治療が試みられてきた。本研究は、星細胞の脱活性化を基盤とする組織修復という、従来とは異なる視点に立って肝線維化の改善と再生促進の病態連繋に関する新たな学問の構築と、新たな肝線維症治療への応用を目指すものである。
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