Development of new treatment methods for primary biliary cholangitis by genome and lipid information from disease mimic culture system
Project/Area Number |
17H04164
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kyushu University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
原田 憲一 金沢大学, 医学系, 教授 (30283112)
中村 稔 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター, 客員研究員 (40217906)
有田 誠 慶應義塾大学, 薬学部(芝共立), 教授 (80292952)
吉住 朋晴 九州大学, 医学研究院, 准教授 (80363373)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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Keywords | 原発性胆汁性胆管炎 / 胆管細胞 / 免疫細胞 / 網羅的アレイ解析 / 脂質情報 / 疾患模倣培養系 / ゲノムワイド関連解析 / 網羅的遺伝子解析 / 網羅的資質解析 / PBC / GWA / 免疫学 / 脂質メディエーター / 病態模倣培養系 |
Outline of Final Research Achievements |
While production of interferon g (IFNG) is increased in primary biliary cholangitis (PBC), IFNG sensitivity of biliary epithelial cells (BEC) was not changed. And 9 inflammation related genes were extracted as increased expression genes in BEC from PBC. Among these 9 genes, immune staining was available for 4 genes encoding proteins, and these 4 proteins expression was increased in BEC from PBC, and these expressions were correlated to cholangitis activities. Furthermore from lipid information, prostaglandin E2 (PGE2) that is produced from the contact of BEC with immune cells had immune regulatory function, and it was clarified that IFNG production from immune cells increase in case of the suppression of PGE2 production by indomethacin.
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Academic Significance and Societal Importance of the Research Achievements |
PBCで病態を修飾する鍵分子の一つとして免疫細胞が産生するIFNGの役割が明らかになり、新たな疾患バイオマーカー・治療標的分子として注目されるようになった。今後、細胞障害活性が強い胆汁酸刺激を緩和するといった標準治療には抵抗を示す症例を中心に、IFNG下流シグナルを制御するJAK/STAT阻害剤を用いた新たな治療法の展開が可能である。さらに胆管細胞で発現亢進する炎症関連タンパク質の機能を調べることで、標的細胞からの抗炎症・線維化治療の開発が期待できる。また遺伝子にコードされない脂質代謝の観点からも炎症制御研究が展開できることが示された。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Kawano A, Shigematsu H, Miki K, Ichiki Y, Morita C, Yanagita K, Takahashi K, Dohmen K, Nomura H, Ishibashi H, Shimoda S.2018
Author(s)
Kawano A, Shigematsu H, Miki K, Ichiki Y, Morita C, Yanagita K, Takahashi K, Dohmen K, Nomura H, Ishibashi H, Shimoda S.
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Journal Title
Intern Med.
Volume: 57(11)
Pages: 1533-1542
Related Report
Peer Reviewed / Open Access
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[Journal Article] Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment.2018
Author(s)
Ogawa E, Furusyo N, Nomura H, Dohmen K, Higashi N, Takahashi K, Kawano A, Azuma K, Satoh T, Nakamuta M, Koyanagi T, Kato M, Shimoda S, Kajiwara E, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group
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Journal Title
Aliment Pharmacol Ther.
Volume: 47(1)
Pages: 104-113
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nishida N, Aiba Y, Hitomi Y, Kawashima M, Kojima K, Kawai Y, Ueno K, Nakamura H, Yamashiki N, Tanaka T, Tamura S, Mori A, Yagi S, Soejima Y, Yoshizumi T, Takatsuki M, Tanaka A, Harada K, Shimoda S, Komori A, Eguchi S, Maehara Y, Uemoto S, Kokudo N, Nagasaki M, Tokunaga K, Nakamura M2018
Author(s)
Nishida N, Aiba Y, Hitomi Y, Kawashima M, Kojima K, Kawai Y, Ueno K, Nakamura H, Yamashiki N, Tanaka T, Tamura S, Mori A, Yagi S, Soejima Y, Yoshizumi T, Takatsuki M, Tanaka A, Harada K, Shimoda S, Komori A, Eguchi S, Maehara Y, Uemoto S, Kokudo N, Nagasaki M, Tokunaga K, Nakamura M
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Journal Title
Sci Rep.
Volume: 8(1)
Pages: 8071-8071
Related Report
Peer Reviewed / Open Access
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[Journal Article] Increased expression and altered localization of cathepsin Z are associated with progression to jaundice stage in primary biliary cholangitis2018
Author(s)
Aiba Y, Harada K, Ito M, Suematsu T, Aishima S, Hitomi Y, Nishida N, Kawashima M, Takatsuki M, Eguchi S, Shimoda S, Nakamura H, Komori A, Abiru S, Nagaoka S, Migita K, Yatsuhashi H, Tokunaga K, Nakamura M
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Journal Title
Sci Rep
Volume: 8(1)
Pages: 11808-11808
Related Report
Peer Reviewed / Open Access
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[Journal Article] Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A multicenter, real-world cohort study focusing on chronic kidney disease2018
Author(s)
Ogawa E, Furusyo N, Azuma K, Nakamuta M, Nomura H, Dohmen K, Satoh T, Kawano A, Koyanagi T, Ooho A, Takahashi K, Kato M, Shimoda S, Kajiwara E, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group
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Journal Title
Antiviral Res.
Volume: 159
Pages: 143-152
Related Report
Peer Reviewed / Open Access
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