IL33/ST2 pathway involvement in the pathogenesis and disease progression of primary biliary cholangitis

• Project/Area Number: 16K21069
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology; Immunology
• Research Institution: Shinshu University
• Principal Investigator: JOSHITA SATORU 信州大学, 学術研究院医学系, 助教 (90597965)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 原発性胆汁性胆管炎 / IL-33 / ST2 / Autotaxin / sST2 / 原発性胆汁性肝硬変 / 病態 / 予後

Outline of Final Research Achievements

Primary biliary cholangitis (PBC) is a slowly progressive liver-specific autoimmune disease. The pathogenesis and mechanism of PBC progression are incompletely understood. The key findings of this study were as follows; 1) the IL33/ST2 pathway was associated not only with pathogenesis, but also with disease progression, in patients with PBC. 2) Serum Autotaxin values appear to be useful for assessing disease stage and prognosis in PBC.

Research Products

• [Journal Article] Genetics and epigenetics in the pathogenesis of primary biliary cholangitis (2018)
  • Author(s): Joshita Satoru、Umemura Takeji、Tanaka Eiji、Ota Masao
  • Journal Title: Clinical Journal of Gastroenterology Volume: 11 Issue: 1 Pages: 11-18
  • DOI: 10.1007/s12328-017-0799-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum Autotaxin Is a Useful Disease Progression Marker in Patients with Primary Biliary Cholangitis (2018)
  • Author(s): Joshita Satoru、Umemura Takeji、Usami Yoko、Yamashita Yuki、L. Norman Gary、Sugiura Ayumi、Yamazaki Tomoo,Fujimori Naoyuki、Kimura Takefumi、Matsumoto Akihiro、Igarashi Koji、Yoshizawa Kaname、Ota Masao、Tanaka Eiji
  • Journal Title: Scientific Reports Volume: 印刷中
  • NAID: 120007099792
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Contribution to the Pathogenesis of Primary Biliary Cholangitis. (2017)
  • Author(s): Joshita S, Umemura T, Tanaka E, Ota M.
  • Journal Title: J Immunol Res Volume: 2017 Pages: 3073504-3073504
  • DOI: 10.1155/2017/3073504
  • NAID: 120007100138
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. (2017)
  • Author(s): Kawashima M, Honda M, Nakamura M. et al.
  • Journal Title: Hum Mol Genet. Volume: - Pages: 650-659
  • DOI: 10.1093/hmg/ddw406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between serum soluble CD14 and IL-8 levels and clinical outcome in primary biliary cholangitis (2017)
  • Author(s): Umemura, T. Sekiguchi, T. Joshita, S. Yamazaki, T. Fujimori, N. Shibata, S. Ichikawa, Y. Komatsu, M. Matsumoto, A. Shums, Z. Norman, G. L. Tanaka, E. Ota, M.
  • Journal Title: Liver International Volume: 印刷中 Issue: 6 Pages: 897-905
  • DOI: 10.1111/liv.13316
  • NAID: 120007100137
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan. (2016)
  • Author(s): Umemura T, Joshita S, Yamazaki T, Komatsu M, Katsuyama Y, Yoshizawa K, Tanaka E, Ota M
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 29770-29770
  • DOI: 10.1038/srep29770
  • NAID: 120007100139
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Liver stiffness-spleen size-to-platelet ratio risk score detects esophageal varices in chronic liver disease. (2016)
  • Author(s): Shibata S, Joshita S, Umemura T, Yamazaki T, Fujimori N, Ichikawa Y, Komatsu M, Matsumoto A, Tanaka E.
  • Journal Title: Springerplus Volume: 5 Issue: 1 Pages: 998-998
  • DOI: 10.1186/s40064-016-2708-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Asymptomatic and symptomatic states are independent risk factors predicting PBC long-term outcome (2017)
  • Author(s): Joshita Satoru、Umemura Takeji、Tanaka Eiji
  • Organizer: The Asian Pacific Association for the Study of the Liver Single Topic Conference 2017
  • Int'l Joint Research
• [Presentation] IL33/ST2 pathway involvement in the pathogenesis and disease progression of primary biliary cholangitis (2017)
  • Author(s): Joshita Satoru、Umemura Takeji、Matsumoto Akihiro、Yoshizawa Kaname、Ota Masao、Tanaka Eiji
  • Organizer: Digestive Disease Week 2017
  • Int'l Joint Research
• [Presentation] Association of Serum Autotaxin Level with Disease Stage in Japanese Patients with Primary Biliary Cholangitis (2017)
  • Author(s): Joshita Satoru、Umemura Takeji、Yoko Usami、Sugiura Ayumi、Yamazaki Tomoo、Fujimori Naoyuki、Komatsu Michiharu、Matsumoto Akihiro、Igarashi Koji、Ota Masao、Tanaka Eiji
  • Organizer: The Asian Pacific Digestive week 2017
  • Int'l Joint Research
• [Presentation] 原発性胆汁性胆管炎における血中Autotaxinの臨床的意義の検討 (2017)
  • Author(s): 城下智、梅村武司、田中榮司
  • Organizer: 第25回日本消化器関連学会週間
  • Int'l Joint Research
• [Presentation] 原発性胆汁性胆管炎の線維化進行と病態進展におけるIL-33/ST2 pathwayの役割 (2016)
  • Author(s): 城下 智、梅村 武司、田中 榮司
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 東京、京王プラザホテル
  • Year and Date: 2016-12-08
• [Presentation] PTPN22遺伝子多型は自己免疫性肝疾患の疾患抵抗性と関連する (2016)
  • Author(s): 城下智、梅村武司、山崎智生、齊藤博美、平山敦大、赤羽由紀、山崎麻美、田中栄司、勝山善彦、太田正穂
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 札幌、北海道大学学術交流会館
  • Year and Date: 2016-10-22
• [Presentation] Liver Stiffness-Spleen Size-to-Platelet Ratio Risk Score Identifies Esophageal Varices in Chronic Liver Disease (2016)
  • Author(s): Joshita S, Shibata S, Umemura T, Sugiura A, Yamazaki S, Fujimori N, Ichikawa Y, Komatsu M, Matsumoto A, Tanaka E.
  • Organizer: HCV 2016 23rd International Symposium on Hepatitis C Virus and Related Viruses （国際学会）
  • Place of Presentation: Kyoto, Kyoto International Conference Center
  • Year and Date: 2016-10-11
  • Int'l Joint Research
• [Presentation] 無症候性および症候性原発性胆汁性肝硬変の予後解析 (2016)
  • Author(s): 城下 智、梅村 武司、吉澤 要、田中 榮司
  • Organizer: 第113回日本内科学会講演会
  • Place of Presentation: 東京、東京国際フォーラム
  • Year and Date: 2016-04-15