2018 Fiscal Year Final Research Report
Basic research for novel approaches to liver diseases, derived from studies on ductular reaction and SOX9 in biliary atresia
| Project/Area Number |
16K11349
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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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| Research Field |
Pediatric surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
Inomata Yukihiro 熊本大学, 医学部附属病院, 非常勤診療医師 (50193628)
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| Co-Investigator(Kenkyū-buntansha) |
磯野 香織 熊本大学, 医学部附属病院, 非常勤診療医師 (10756258)
本田 正樹 熊本大学, 医学部附属病院, 病院教員 (80573609)
吉井 大貴 熊本大学, 医学部附属病院, 非常勤診療医師 (00792582)
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| Research Collaborator |
Shimata Keita
Kadohisa Masashi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | SOX9 / 細胆管反応 / 胆道閉鎖症 / 慢性肝疾患 / TROP2 / 胆汁うっ滞 / 葛西手術 |
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| Outline of Final Research Achievements |
Ductular reaction (DR) has been thought that it has crucial roles in liver regeneration and the etiology of liver fibrosis, however, the exact mechanism of DR is still unknown. We hypothesized on the basis of our previous studies that SOX9 may be an important factor in the development of DR. Then, we analyzed the association between DR and SOX9 by experimental liver injury using SOX9 knockout mice and immunohistological staining using human and mouse liver specimens. In mouse experiments, we found that the development of DR was more inhibited especially in cholestatic injury of SOX9 KO mouse than the wild type mouse, and the development of fibrosis was also inhibited. In human specimens with DR, SOX9 localization of liver specimens with primary biliary cholangitis was different from liver specimens with other liver diseases. Some kind of mechanisms of injured nuclear localization of SOX9 might result in the difference of pathological conditions between liver diseases.
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| Free Research Field |
小児外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、SOX9が、マウスでみられるDRの進展だけでなく、それに付随して見られる肝線維化の進展にも重要である可能性があることが分かった。これは、細胆管反応を伴う様々な慢性肝疾患において、病態の進行を抑制する目的として、SOX9をターゲットとした治療の足がかりとなる結果と考える。また、未だ病因が不明確な肝疾患が多い中、SOX9の局在が特徴的な肝疾患では、SOX9発現のさらなる解析によって、病因の特定につながる可能性もあると考える。
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