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Elucidation of the pathology and treatment of refractory small intestinal ulcer disease using genetically engineered mouse and PG mass spectrometry

Research Project

Project/Area Number 15H04811
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKyorin University

Principal Investigator

HISAMATSU TADAKAZU  杏林大学, 医学部, 教授 (60255437)

Co-Investigator(Kenkyū-buntansha) 杉浦 悠毅  慶應義塾大学, 医学部(信濃町), 特任講師 (30590202)
金井 隆典  慶應義塾大学, 医学部(信濃町), 教授 (40245478)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords小腸潰瘍 / プロスタグランジン / SLCO2A1 / CEAS / 遺伝性小腸潰瘍症 / 質量分析 / マウスモデル
Outline of Final Research Achievements

For the diagnosis of a patient with a CEAS patient, a simple diagnostic technique by SLCO 2A1 protein fluorescent immunostaining method was established. For functional analysis of SLCO2A1 mutant protein found in patients, a gene transfer system by Xenopus oocytes was set up and as a result of the transport experiment of PG, Mutations that completely lost function and mutations that only partially declined in function were observed. Furthermore, it was shown that female sex hormone influences PG transporting ability. We established vascular endothelial specific SLCO2A1 deficient mice and established a mass spectrometry method of PG metabolism analysis system in mouse small intestine. As a result, changes in PG metabolism in each small intestinal ulcer model including genetically modified mice could be observed.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease.2018

    • Author(s)
      Umeno J, Esaki M, Hirano A, Fuyuno Y, Ohmiya N, Yasukawa S, Hirai F, Kochi S, Kurahara K, Yanai S, Uchida K, Hosomi S, Watanabe K, Hosoe N, Ogata H, Hisamatsu T, Nagayama M, Yamamoto H, Abukawa D, Kakuta F, Onodera K, Matsui T, Hibi T, Yao T, Kitazono T, Matsumoto T;CEAS study group.
    • Journal Title

      J Gastroenterol

      Volume: Jan 8 Issue: 8 Pages: 907-915

    • DOI

      10.1007/s00535-017-1426-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an Enteric Disorder to be Considered in the Differential Diagnosis of Crohn’s Disease2017

    • Author(s)
      Hosoe Naoki、Ohmiya Naoki、Yano Tomonori、Okita Yoshiki、Araki Toshimitsu、Saruta Masayuki、Ohtsuka Kazuo、CEAS Atlas Group
    • Journal Title

      Journal of Crohn's and Colitis

      Volume: 11 Issue: 10 Pages: 1277-1281

    • DOI

      10.1093/ecco-jcc/jjx068

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 『非特異性多発性小腸潰瘍症/CEAS-遺伝子異常と類縁疾患』 主題研究1.SLCO2A1の機能とその異常2017

    • Author(s)
      久松理一,關 里和
    • Journal Title

      胃と腸

      Volume: 52巻 第11号 Pages: 1453-1457

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 非特異性多発性小腸潰瘍症の難病指定とSLCO2A1関連小腸症2016

    • Author(s)
      小林 拓, 梅野淳嗣, 久松理一, 江崎幹宏, 松井敏幸, 松本主之, 日比紀文
    • Journal Title

      日本消化器病学会雑誌

      Volume: 113(8) Pages: 1380-1385

    • NAID

      130005253859

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集/小腸潰瘍発症メカニズムはどこまで明らかになったか SLCO2A1の機能とプロスタグランジン関連腸症2016

    • Author(s)
      久松理一
    • Journal Title

      GI Research 先端医学社

      Volume: 第24巻5号 Pages: 28-33

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 特集/小腸潰瘍発症メカニズムはどこまで明らかになったか 非特異性多発性小腸潰瘍症(CEAS)の発症メカニズム2016

    • Author(s)
      梅野淳嗣,江崎幹宏,久松理一,河内修司,蔵原晃一,安川重義,平井郁仁,松井敏幸,八尾恒良,北園孝成,松本主之
    • Journal Title

      GI Research 先端医学社

      Volume: 第24巻5号 Pages: 20-27

    • Related Report
      2016 Annual Research Report
  • [Journal Article] A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter.2015

    • Author(s)
      Umeno J, Hisamatsu T, Esaki M, Atsushi Hirano A, Kubokura N, Asano K, Kochi S, Yanai S, Fuyuno Y, Shimamura K, Hosoe N, Ogata H, Watanabe T, Aoyagi K, Ooi H, Watanabe K, Yasukawa S, Hirai F, Matsui T, Iida M, Yao T, Hibi T, Kosaki K, Kanai T, Kitazono T, Matsumoto T.
    • Journal Title

      PLoS Genetics

      Volume: Nov 5;11(11): Issue: 11 Pages: 1-15

    • DOI

      10.1371/journal.pgen.1005581

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Identification of a novel disease entity, chronic enteropathy associated with SLCO2A1 (CEAS)2017

    • Author(s)
      Hisamatsu T, Umeno J, Matsumoto T
    • Organizer
      The 10th International Gastointestinal Consensus Symposium
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification ofa novel disease entity, chronic enteropathy associated with SLCO2A1 (CEAS)2017

    • Author(s)
      Hisamatsu T, Umeno J, Matsumoto T.
    • Organizer
      The 10th International Gastointestinal Consensus Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特別講演 非特異性多発性小腸潰瘍症の原因遺伝子同定から学んだこと  若手消化器内科Dr.へのメッセージ2016

    • Author(s)
      久松理一
    • Organizer
      日本消化器病学会関東支部 第341回例会
    • Place of Presentation
      東京 海運クラブ
    • Year and Date
      2016-09-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] SLCO2A1発現解析を用いた非特異性多発性小腸潰瘍症の診断と病態解明へアプローチ2016

    • Author(s)
      久松理一,島村克好,細江直樹,杉浦悠毅,高橋信一,金井隆典
    • Organizer
      第12回日本消化管学会総会学術集会
    • Place of Presentation
      東京 京王プラザホテル
    • Year and Date
      2016-02-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 質量分析法を用いたNSAIDs起因性小腸潰瘍の小腸粘膜PG代謝物の網羅的解析による病態解明と今後の展望2015

    • Author(s)
      久松理一,島村克好,金井隆典,高橋信一,杉浦悠毅
    • Organizer
      第53回小腸研究会
    • Place of Presentation
      盛岡
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低用量アスピリン起因性小腸粘膜障害に対する腸溶性カプセルに充填したエカベナトリウムの効果についての検討.健常人を対象とし,カプセル内視鏡を用いた二重盲検,クロスオーバー,パイロット試験2015

    • Author(s)
      林田真理,久松理一,高橋信一
    • Organizer
      JDDW 2015
    • Place of Presentation
      東京
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非特異性多発性小腸潰瘍症の診断における内視鏡下生検の意味 ワークショップ7 希少難治性消化管疾患における内視鏡の役割2015

    • Author(s)
      久松理一,細江直樹,金井隆典
    • Organizer
      第89回日本消化器内視鏡病学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] SLOCO2A1変異によるPG輸送障害と非特異性多発性小腸潰瘍症2015

    • Author(s)
      久松理一,細江直樹,金井隆典
    • Organizer
      第101回日本消化器病学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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