Comprehensive study to elucidate molecular mechanisms behind intrahepatic cholestasis

• Project/Area Number: 22590746
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokai University
• Principal Investigator: KAGAWA Tatehiro 東海大学, 医学部, 准教授 (30245469)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 胆汁酸トランスポーター / 胆汁うっ滞 / 胆汁分泌 / ウルソデオキシコール酸 / 胆汁酸 / トランスポーター / 膜タンパク

Research Abstract

Intrahepatic cholestasis is a difficult-to-treat disease. Although ursodeoxycholic acid has choleretic effect and is widely used to treat cholestasis, molecular mechanisms behind this effect remain unknown. In this study we demonstrated that ursodeoxycholic acid induces choleresis by stabilizing bile salt export pump in the apical membrane.

Research Products

• [Journal Article] Partial splenic embolization using n-butyl cyanoacrylate: intraprocedural evaluation by magnetic resonance imaging (2013)
  • Author(s): Koizumi J, Kagawa T, et al
  • Journal Title: Eur Radiol Volume: 23(5) Pages: 1429-42
  • Peer Reviewed
• [Journal Article] Meloxicam as an adjuvant to peginterferon alfa-2a and ribavirin treatment for genotype 1 chronic hepatitis C: a randomized trial. (2013)
  • Author(s): Tatehiro Kagawa
  • Journal Title: Hepatol Research Volume: 未確定 Issue: 9 Pages: 925-932
  • DOI: 10.1111/hepr.12046
  • Peer Reviewed
• [Journal Article] Carbon Dioxide (CO2) vs Iodinated Contrast Digital Subtraction Angiography during Balloon-occluded Retrograde Transvenous Obliteration (BRTO) Using Foam Sclerosant for Gastric Varices (2012)
  • Author(s): Koizumi J, Kagawa T, et al
  • Journal Title: J Vasc Interv Radiol Volume: 23 Pages: 1453-1459
  • Peer Reviewed
• [Journal Article] Complete Response after Short-Term Sorafenib Treatment in a Patient with Lymph Node Metastasis of Hepatocellular Carcinoma (2012)
  • Author(s): Mizukami H, Kagawa T, et al
  • Journal Title: Case Rep Oncol Volume: 5 Issue: 2 Pages: 380-384
  • DOI: 10.1159/000341259
  • Peer Reviewed
• [Journal Article] Type 1 gastric cancer presenting as protein-losing gastroenteropathy and ball-valve syndrome (2012)
  • Author(s): Hirose S, Kagawa T, et al
  • Journal Title: Dig Endosc Volume: 24 Issue: 1 Pages: 55-55
  • DOI: 10.1111/j.1443-1661.2011.01164.x
  • Peer Reviewed
• [Journal Article] Balloon-occluded retrograde transvenous obliteration of gastric varices: use of CT-guided foam sclerotherapy to optimize technique (2012)
  • Author(s): Koizumi J, Kagawa T, et al(7名).
  • Journal Title: AJR Am J Roentgenol Volume: 199(1) Pages: 200-7
  • Peer Reviewed
• [Journal Article] Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial. (2012)
  • Author(s): Kagawa T, et al
  • Journal Title: Hepatol Res Volume: 42(4) Pages: 351-358
  • NAID: 10031144247
  • Peer Reviewed
• [Journal Article] Involvement of multiple elements inFXR-mediated transcriptional activationof FGF19 (2012)
  • Author(s): Miyata M, Kagawa T, et al
  • Journal Title: J Steroid Biochem Mol Biol Volume: 132(1-2) Pages: 41-47
  • Peer Reviewed
• [Journal Article] Effect of endothelin a receptor antagonist on hepatic hemodynamics in cirrhotic rats. Implications for endothelin-1 in portal hypertension (2012)
  • Author(s): Takashimizu S, Kagawa T, et al
  • Journal Title: Tokai J Exp Clin Med Volume: 36(2) Pages: 37-43
  • Peer Reviewed
• [Journal Article] Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial. (2012)
  • Author(s): Tatehiro Kagawa
  • Journal Title: Hepatol Research Volume: 42 Issue: 4 Pages: 351-358
  • DOI: 10.1111/j.1872-034x.2011.00944.x
  • NAID: 10031144247
  • Peer Reviewed
• [Journal Article] C-arm CT-guided foam sclerotherapy for the treatment of gastric varices (2010)
  • Author(s): Koizumi J, Kagawa T, , et al
  • Journal Title: J Vasc Interv Radiol Volume: 21(10) Pages: 1583-7
  • Peer Reviewed
• [Journal Article] Transcatheter arterial chemoembolization plus radiofrequency ablation therapy for early stage hepatocellular carcinoma: comparison with surgical resection (2010)
  • Author(s): Kagawa T, et al
  • Journal Title: Cancer 2010 Volume: 116 Pages: 3638-44
  • Peer Reviewed
• [Journal Article] Differential Impact of Adherence to Pegylated Interferon and Ribavirin in the Treatment of Genotype 1 High Viral (2010)
  • Author(s): Numata M, Kagawa T, et al
  • Journal Title: Titer Chronic Hepatitis C 2010 Volume: 702748 Pages: 1-6
  • DOI: 10.1155/2010/702748
  • Peer Reviewed
• [Journal Article] Long-term effects of antiviral therapy in patients with chronic hepatitis C (2010)
  • Author(s): Kagawa T, Keeffe EB
  • Journal Title: Hepatitis Research and Treatment 2010 Volume: 562578 Pages: 1-9
  • DOI: 10.1155/2010/562578
  • Peer Reviewed
• [Journal Article] Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membranein MDCK II cells.
  • Author(s): Kagawa T, et al
  • Journal Title: J Gastroenterol Volume: (in press)
  • Peer Reviewed
• [Presentation] 胆汁うっ滞症におけるABCB11 V444A polymorphismとHLA genotypeの解析 (2012)
  • Author(s): 鶴谷康太、加川建弘
  • Organizer: 第34回胆汁酸研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-12-01
• [Presentation] 肝内胆汁うっ滞症におけるBSEP SNPの解析.ワークショップ:肝臓における薬物代謝研究の展開 (2012)
  • Author(s): 加川建弘
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] Impact of ABCB11 V444A polymorphism and HLA genotype on susceptibility to drug-induced cholestasis in Japan. (2012)
  • Author(s): Tatehiro Kagawa
  • Organizer: 63nd Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston
• [Presentation] COX-2 inhibitor enhances the efficacy of peginterferon-alfa 2a and ribavirin combination therapy for chronic hepatitis C. (2012)
  • Author(s): Tatehiro Kagawa
  • Organizer: 63nd Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston
• [Presentation] Meloxicam as an adjuvant to peginterferon alfa-2a and ribavirin treatment for genotype 1 hepatitis C: a randomized trial. (2012)
  • Author(s): Tatehiro Kagawa
  • Organizer: he 10th JSH Single topic conference “Hepatitis C: Best practice based on science”
  • Place of Presentation: Tokyo
• [Presentation] 肝内胆汁うっ滞症におけるBSEP SNPの解析 (2012)
  • Author(s): 加川建弘
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] 当院における薬物性肝障害症例の解析 (2012)
  • Author(s): 荒瀬吉孝
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京
• [Presentation] 当院における36年間の急性肝不全、遅発性肝不全患者の解析 (2012)
  • Author(s): 広瀬俊治
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京
• [Presentation] 胆汁酸動態の調節因子であるヒト回腸 FGF19は複数のFXR応答領域を介して転写調節される (2011)
  • Author(s): 宮田昌明、畑竜也、加川建弘
  • Organizer: 第33回胆汁酸研究会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-19
• [Presentation] UDCAによるbile salt export pump活性化機序の解析 (2010)
  • Author(s): 加川建弘
  • Organizer: 第32回胆汁酸研究会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-06
• [Presentation] Ursodeoxycholic acid activates bile salt export pump stably expressed in MDCK II cells. (2010)
  • Author(s): Tatehiro Kagawa
  • Organizer: 第61回アメリカ肝臓学会
  • Place of Presentation: ボストン
  • Year and Date: 2010-11-01
• [Presentation] ウルソデオキシコール酸による胆汁酸トランスポーター活性化機序の解析 (2010)
  • Author(s): 加川建弘
  • Organizer: 第6回東日本胆汁酸研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-31
• [Presentation] ウルソデオキシコール酸による胆汁酸トランスポーター活性化機序の解析 (2010)
  • Author(s): 加川建弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-28
• [Presentation] Ursodeoxycholic acid activates bile salt export pump stably expressed in MDCK II cells (2010)
  • Author(s): Kagawa T
  • Organizer: 61st Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston, USA
• [Presentation] 胆汁酸トランスポーターにおける糖鎖修飾の意義 -肝硬変症における胆汁うっ滞との関係-.ワークショップ1(胆汁酸と生体機能調節、疾患との関わり) (2010)
  • Author(s): 加川建弘、渡辺勲史、峯徹哉
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 横浜
• [Presentation] UDCAによるbile salt export pump活性化機序の解析 (2010)
  • Author(s): 加川建弘
  • Organizer: 第5回トランスポーター研究会
  • Place of Presentation: 東京
• [Presentation] UDCAによる胆汁酸トランスポーター活性化機序の解析 (2010)
  • Author(s): 加川建弘
  • Organizer: 第9回生体機能研究会
  • Place of Presentation: 箱根
• [Presentation] 肝内胆汁うっ滞症におけるABCB11 V444A polymorphismとHLA genotypeの解析
  • Author(s): 鶴谷康太
  • Organizer: 第34回胆汁酸研究会
  • Place of Presentation: 名古屋