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 |
Section | 一般 |
Research Field |
Pediatric surgery
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Research Institution | Kumamoto University |
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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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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 / SOX9遺伝子 / 実験的肝障害 / SOX9ノックアウトマウス / Sox9遺伝子 / 肝障害 |
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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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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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Hydrogen-rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation.2019
Author(s)
Uto K, Sakamoto S, Que W, Shimata K, Hashimoto S, Sakisaka M, Narita Y, Yoshii D, Zhong L, Komohara Y, Li XK, Inomata Y, Hibi T
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Journal Title
BMC Gastroenterol
Volume: 19
Issue: 1
Pages: 25-25
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation2017
Author(s)
Honda M, Sugawara Y, Watanabe T, Tateyama M, Tanaka M, Uchida K, Kawabata S, Yoshii D, Miura K, Isono K, Hayashida S, Ohya Y, Yamamoto H, Sasaki Y, Inomata Y
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Journal Title
Hepatology Research
Volume: -
Issue: 11
Pages: 1147-1154
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 小児肝悪性腫瘍に対する肝移植の役割と課題2017
Author(s)
猪股裕紀洋
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Journal Title
The Japanese Journal of Pediatric Hematology / Oncology
Volume: 54
Issue: 3
Pages: 219-223
DOI
NAID
ISSN
2187-011X, 2189-5384
Related Report
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[Journal Article] Antibody-mediated rejection after ABO-incompatible pediatric living donor liver transplantation for propionic acidemia: A case report.2016
Author(s)
Honda M, Sakamoto S, Sakamoto R, Matsumoto S, Irie T, Uchida K, Shimata K, Kawabata S, Isono K, Hayashida S, Yamamoto H, Endo F, Inomata Y.
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Journal Title
Pediatric Transplantation
Volume: 20
Issue: 6
Pages: 840-845
DOI
Related Report
Peer Reviewed
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[Presentation] Ki67 (MIB-1) indexによる胆道閉鎖症の葛西手術後の予後予測2018
Author(s)
吉井大貴, 猪股 裕紀洋, 嶋田 圭太, 平尾 洸樹, 入江 友章, 伊吹 省, 門久 政司, 川端 誠一, 成田 泰子, 本田 正樹, 林田 信太郎, 大矢 雄希, 山本 栄和, 山本 裕俊, 菅原 寧彦, 菰原 義弘, 日比 泰造
Organizer
第45回日本胆道閉鎖症研究会
Related Report
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[Presentation] 小児移植後長期経過例の諸問題 小児肝移植症例における長期経過後の再移植症例の検討2018
Author(s)
林田 信太郎, 平尾 洸樹, 入江 友章, 門久 政司, 川端 誠一, 嶋田 圭太, 成田 泰子, 本田 正樹, 大矢 雄希, 山本 栄和, 山本 裕俊, 菅原 寧彦, 日比 泰造, 猪股 裕紀洋
Organizer
第54回日本移植学会総会
Related Report
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[Presentation] マウス肝切除モデルを用いた肝再生におけるmicroRNA221の役割の検討2018
Author(s)
大矢 雄希, 津川 大介, 増崎 亮太, 平尾 洸樹, 入江 友章, 嶋田 圭太, 成田 泰子, 磯野 香織, 本田 正樹, 林田 信太郎, 山本 栄和, 山本 裕俊, 菅原 寧彦, 日比 泰造, 猪股 裕紀洋, Karp Seth
Organizer
第54回日本移植学会総会
Related Report
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[Presentation] 当院における胆道閉鎖症に対する生体肝移植術の成績 -移植時年齢の影響について-2016
Author(s)
橋本晋太朗,本田正樹,内田皓士,嶋田圭太,吉井大貴,磯野香織,林田信太郎,大矢雄希,山本栄和,阪本靖介,猪股裕紀洋
Organizer
第53回日本小児外科学会学術集会
Place of Presentation
福岡
Year and Date
2016-05-24
Related Report
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[Presentation] Current status of primary liver transplantation for biliary atresia in Japan2016
Author(s)
Keiichi Uto, Shintaro Hashimoto, Masataka Sakisaka, Daiki Yoshii, Yasuko Narita, Koushi Uchida, Seiichi Kawabata, Keita Shimata, Kaori Isono, Masaki Honda, Shintaro Hayashida, Yuki Oya, Hidekazu Yamamoto, Seisuke Sakamoto, Yukihiro Inomata
Organizer
49th Annual Meeting of the Pacific Association of Pediatric Surgeons
Place of Presentation
Koloa, Hawaii
Year and Date
2016-04-27
Related Report
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