Development of new therapy for liver disease by regulating cellular senescence
| Project/Area Number |
18K06985
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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 49020:Human pathology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 病理学 / 原発性胆汁性胆管炎 / 自己免疫性疾患 / 細胞老化 |
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| Outline of Final Research Achievements |
The hypothesis: “Removing senescent cells (senolysis) may be a novel effective therapy for primary biliary cholangitis (PBC)” was verified in this study. This study revealed that cellular senescence was frequently observed in biliary epithelial cells in small bile ducts and bile ductules in PBC and that the degree of cellular senescence was associated with the stage and activity of PBC and inadequate response to UDCA. Furthermore, cell culture study disclosed that senescence-associated molecules upregulated in biliary epithelial cells in PBC, such as Bcl-xL and IFIT3, could be novel therapeutic targets by senolytic drugs and siRNA.
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| Academic Significance and Societal Importance of the Research Achievements |
PBCの国内患者数は5-6万人と推定されており,約30-40%のUDCA無効例に対する新しい治療薬の開発基盤の確立は意義がある。本研究では, PBCにおける胆管細胞老化は, 病期, 活動性, UDCA治療不応性に関連することを明らかにした。また, 細胞老化関連分子Bcl-xLやIFIT3などは,老化細胞除去薬やsiRNAなどを用いた老化細胞除去の有効な標的となった。本研究は, PBCの新しい治療法として老化細胞除去療法が有望である可能性を示した。
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma: Supportive evidence for the efficacy of immune checkpoint inhibitor therapy2020
Author(s)
Sato Yasunori, Tanaka Shogo, Kinoshita Masahiko, Takemura Shigekazu, Shinkawa Hiroji, Kokudo Takashi, Hasegawa Kiyoshi, Tanaka Hiromu, Yoshimoto Hidero, Mori Akira, Yamamura Minako, Sasaki Motoko, Harada Kenichi, Kubo Shoji
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Journal Title
Journal of Hepato-Biliary-Pancreatic Sciences
Volume: 27
Pages: 860-869
DOI
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Peer Reviewed / Open Access
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[Journal Article] Fulminant myocarditis and pulmonary cavity lesion induced by disseminated mucormycosis in a chronic hemodialysis patient: Report of an autopsied case.2020
Author(s)
Fujisawa Y, Hara S, Zoshima T, Maekawa N, Inoue D, Sasaki M, Gamou T, Nagata Y, Hayashi K, Takeji A, Ito K, Mizushima I, Fujii H, Kawano M.
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Journal Title
Pathology International
Volume: Aug;70(8)
Pages: 557-562
DOI
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Peer Reviewed
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[Presentation] 若年男性に発症したbeta-catenin活性化型肝細胞腺腫の1例2018
Author(s)
米田 憲秀, 北尾 梓, 小坂 一斗, 出雲崎 晃, 小森 隆弘, 井上 大, 蒲田 敏文, 小林 聡, 山口 貴久, 高村 博之, 太田 哲生, 大坪公士郎, 中村律子, 佐々木素子
Organizer
第 32 回日本腹部放射線学会
Related Report
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