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Elucidation of the fibrotic mechanism of HSP47 for the treatment of intestinal fibrosis in Crohn's disease

Research Project

Project/Area Number 16K19150
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

HONZAWA Yusuke  京都大学, 医学研究科, 特定病院助教 (90737884)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords炎症性腸疾患 / クローン病 / heat shock protein 47 / 腸管線維化 / Heat shock protein 47 / 免疫学 / 炎症 / 線維化
Outline of Final Research Achievements

We focused on heat shock protein (HSP) 47 in intestinal fibrosis in Crohn's disease, and examined its mechanism with human samples. As a result, IL-1β enhanced HSP47 expression in the human intestinal myofibroblast cell line (CCD-18Co) in addition to IL-17A. It is believed that IL-1β expression was induced via inflammasome which was multimeric protein complex. In this study, in the examination of peripheral blood mononuclear cells of CD patients with the Mediterranean fever(MEFV) gene mutation, we confirmed inflammasome activation and induction of IL-1β. This result suggested that multiple cytokine environments such as IL-1β and IL-17A in the intestinal tract of CD patients might be involved in HSP47-mediated intestinal fibrosis.

Academic Significance and Societal Importance of the Research Achievements

クローン病(CD)腸管炎症では、免疫学的な観点から多くの研究が行われ、各種薬剤も登場している。その一方で、患者QOLに影響する腸管線維化の機序解明は未だ十分ではなく、治療薬も存在しない。この為、腸管線維化メカニズムの解析は将来的な治療の可能性を有している。今までのところ線維化疾患に関与するとされているHSP47はCD腸管線維化に関与し、その発現にはIL-17A以外にもIL-1βといった炎症性サイトカインも関与している可能性があり、それら制御に基づく治療の可能性も示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (29 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (26 results) (of which Int'l Joint Research: 12 results)

  • [Journal Article] Tricho-hepato-enteric syndrome with novel SKIV2L gene mutations: A case report.2017

    • Author(s)
      Eitaro Hiejima, Takahiro Yasumi, Hiroshi Nakase, Minoru Matsuura, Yusuke Honzawa, Hirokazu Higuchi, Ikuo Okafuji, Tohru Yorifuji, Takayuki Tanaka, Kazushi Izawa, Tomoki Kawai, Ryuta Nishikomori, Toshio Heike
    • Journal Title

      medicine (baltimore)

      Volume: 96 Issue: 46 Pages: e8601-e8601

    • DOI

      10.1097/md.0000000000008601

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Maternal and fetal outcomes in pregnant Japanese women with inflammatory bowel disease2017

    • Author(s)
      Naoki Minami, Minoru Matsuura, Yorimitsu Koshikawa, Satoshi Yamada, Yusuke Honzawa, Shuji Yamamoto, Hiroshi Nakase.
    • Journal Title

      Intestinal Research

      Volume: 15 Issue: 1 Pages: 90-96

    • DOI

      10.5217/ir.2017.15.1.90

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages2016

    • Author(s)
      Toyonaga T, Matsuura M, Mori K, Honzawa Y, Minami N, Yamada S, Kobayashi T, Hibi T, Nakase H
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 35104-35104

    • DOI

      10.1038/srep35014

    • NAID

      120006318859

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Endoscopic findings to predict therapeutic efficacy of anti-TNF agents on patients with ulcerative colitis2018

    • Author(s)
      Yusuke Honzawa, Minoru Matsuura, Shuji Yamamoto, Makoto Okabe, Hiroki Kitamoto, Satoshi Yamada, Hiroshi Seno
    • Organizer
      The 7th Annual Meeting of Asian Organization for Crohn's & Colitis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Efficacy and safety of thiopurine and allopurinol cotherapy in thiopurine-naive Japanese UC patients2018

    • Author(s)
      Makoto Okabe, Minoru Matsuura, Hiroki Kitamoto, Satoshi Yamada, Yusuke Honzawa, Shuji Yamamoto, Hiroshi Seno
    • Organizer
      The 7th Annual Meeting of Asian Organization for Crohn's & Colitis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact fo advance in medical therapies on clinical outcome in patients with ulcerative colitis concomitant cytomegalovirus infection2018

    • Author(s)
      Hiroki Kitamoto, Shuji Yamamoto, Yusuke Honzawa, Satoshi Yamada, Makoto Okabe, Hiroshi Seno, Minoru Matsuura
    • Organizer
      The 7th Annual Meeting of Asian Organization for Crohn's & Colitis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小腸カプセル内視鏡で診断が困難であった上部小腸腫瘍2例についての検討2018

    • Author(s)
      山田 聡、松浦 稔、岡部 誠、北本 博規、本澤 有介、山本 修司、妹尾 浩
    • Organizer
      第56回日本小腸学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 活動期潰瘍性大腸炎の大腸粘膜におけるEpstein-Barr virus再活性化についての検討2018

    • Author(s)
      山田 聡、山本 修司、松浦 稔、北本 博規、岡部 誠、本澤 有介、妹尾 浩
    • Organizer
      第9回日本炎症性腸疾患学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] サイトメガロウイルス再活性化を伴った潰瘍性大腸炎患者の内視鏡所見と臨床的背景に関する検討2018

    • Author(s)
      北本 博規、松浦 稔、岡部 誠、山田 聡、本澤 有介、山本 修司、妹尾 浩
    • Organizer
      第9回日本炎症性腸疾患研究会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アルコール離脱症状を契機に診断に至った肺動脈内膜肉腫の一例2018

    • Author(s)
      住永 圭一郎、本澤 有介、佐藤 千尋、井口 恵里子、西川 義浩、高橋 健、上田 佳秀、松本 繁巳、武藤 学、妹尾 浩
    • Organizer
      日本内科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] CMV感染合併潰瘍性大腸炎の臨床転帰に関する検討2017

    • Author(s)
      北本 博規、松浦 稔、山本 修司、岡部 誠、越川 頼光、山田 聡、本澤 有介、妹尾 浩
    • Organizer
      第8回 日本炎症性腸疾患学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Long-term outcome of patients with ulcerative colitis after initial tacrolimus rescue therapy2017

    • Author(s)
      Yusuke Honzawa, Minoru Matsuura, Shuji Yamamoto, Satoshi Yamada, Yorimitsu Koshikawa, Makoto Okabe, Hiroki Kitamoto, Hiroshi Seno
    • Organizer
      The5th Annual Meeting of Asian Organization for Crohn`s and Colitis (AOCC)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Early induction of immnunosuppressive agents prior to endoscopic balloon dilatation contributes to avoidance of surgery in patients with Crohn’s disease2017

    • Author(s)
      Makoto Okabe, Minoru Matsuura, Shuji Yamamoto, Yusuke Honzawa, Yorimitsu Koshikawa, Satoshi Yamada, Hiroki Kitamoto, Hiroshi Seno
    • Organizer
      The5th Annual Meeting of Asian Organization for Crohn`s and Colitis (AOCC)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸管局所サイトメガロウイルス感染を伴った潰瘍性大腸炎における大腸内視鏡所見とその臨床転帰との関連性に関する検討2017

    • Author(s)
      北本 博規、本澤 有介、山本 修司、松浦 稔、妹尾 浩
    • Organizer
      第98回日本消化器内視鏡学会 近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当院における潰瘍性大腸炎関連大腸癌の内視鏡サーベイランスに関する検討2016

    • Author(s)
      岡部 誠, 松浦 稔, 本澤 有介, 山本 修司, 妹尾 浩.
    • Organizer
      第97回日本消化器内視鏡学会近畿支部例会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] タクロリムス救済療法(Tacrolimus rescue therapy)が難治性潰瘍性大腸炎の長期経過に与える影響2016

    • Author(s)
      本澤 有介, 松浦 稔, 妹尾 浩.
    • Organizer
      第58回日本消化器病学会大会 (第24回日本消化器病関連学会週間)
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Differential distribution of Cytomegalovirus and Epstein-Barr Virus expression in the colonic mucosa of patients with active ulcerative colitis2016

    • Author(s)
      Satoshi Yamada, Minoru Matsuura, Yusuke Honzawa, Makoto Okabe, Naoki Minami, Yorimitus Koshikawa, Shuji Yamamoto, Hiroshi Seno.
    • Organizer
      Asian Pacific Digestive Week 2016
    • Place of Presentation
      Kobe Convention Center
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ral activation exacerbates colonic inflammation through the impairment of intestinal barrier function in experimental murine colitis2016

    • Author(s)
      Naoki Minami, Minoru Matsuura, Shuji Yamamoto, Yusuke Honzawa, Satoshi Yamada, Yorimitsu Koshikawa, Hiroshi Seno, Hiroshi Nakase, Hisanori Horiuchi.
    • Organizer
      Asian Pacific Digestive Week 2016
    • Place of Presentation
      Kobe Convention Center
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The characteristics and clinical outcomes of ulcerative colitis patients with concomitant cytomegalovirus infection2016

    • Author(s)
      Yorimitsu Koshikawa, Minoru Matsuura, Yusuke Honzawa, Naoki Minami, Shuji Yamada, Hiroshi Seno, Hiroshi Nakase.
    • Organizer
      Asian Pacific Digestive Week 2016
    • Place of Presentation
      Kobe Convention Center
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 重症潰瘍性大腸炎に対するRescue療法としてのInfliximabおよびTacrolimusの治療適正化2016

    • Author(s)
      山本 修司, 松浦 稔, 本澤 有介, 妹尾 浩,
    • Organizer
      第105回 日本消化器病学会近畿支部例会
    • Place of Presentation
      大阪国際交流センター
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 寛解期クローン病患者におけるビタミンK不足と腸内細菌叢の関連性についての検討2016

    • Author(s)
      山田 聡, 松浦 稔, 本澤 有介, 山本修司, 南 尚希, 越川 頼光, 仲瀬 裕志, 妹尾 浩.
    • Organizer
      第53回 日本消化器免疫学会総会
    • Place of Presentation
      ホテルニューオータニ大阪
    • Year and Date
      2016-07-15
    • Related Report
      2016 Research-status Report
  • [Presentation] タクロリムス救済療法(Tacrolimus rescue therapy)が難治性潰瘍性大腸炎の長期経過に与える影響2016

    • Author(s)
      本澤 有介, 松浦 稔, 妹尾 浩.
    • Organizer
      第7回 日本炎症性腸疾患学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinical impact of Tacrolimus rescue therapy for refractory ulcerative colitis2016

    • Author(s)
      Yusuke Honzawa, Minoru Matsuura, Naoki Minami, Satoshi Yamada, Yorimitsu Koshikawa, Hiroshi Seno.
    • Organizer
      The 4th Annual Meeting of Asian Organization for Crohn's and Colitis
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A case report of inflammatory bowel disease-like colitis successfully treated with infliximab in a patient with common variable immunodeficiency2016

    • Author(s)
      Yorimitus Koshikawa, Minoru Matsuura, Yusuke Honzawa, Naoki Minami, Satoshi Yamada, Hiroshi Seno.
    • Organizer
      The 4th Annual Meeting of Asian Organization for Crohn's and Colitis
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 活動期潰瘍性大腸炎の腸管組織におけるEpstein-Barr virus発現についての検討2016

    • Author(s)
      山田 聡, 松浦 稔, 本澤 有介, 南 尚希, 越川 頼光, 妹尾 浩.
    • Organizer
      第7回 日本炎症性腸疾患学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 当院で経験した炎症性腸疾患合併妊娠23例の臨床的検討2016

    • Author(s)
      南 尚希, 松浦 稔, 本澤 有介, 越川 頼光, 山田 聡, 妹尾 浩.
    • Organizer
      第7回 日本炎症性腸疾患学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Differential distribution of Cytomegalovirus and Epstein-Barr Virus expression in the colonic mucosa of patients with active ulcerative colitis2016

    • Author(s)
      Satoshi Yamada, Minoru Matsuura, Yusuke Honzawa, Naoki Minami, Yorimitsu Koshikawa, Hiroshi Nakase.
    • Organizer
      The 4th Annual Meeting of Asian Organization for Crohn's and Colitis
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2016-07-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Management of Japanese pregnant patients with inflammatory bowel disease from our experienced 23 cases2016

    • Author(s)
      Naoki Minami, Minoru Matsuura, Yusuke Honzawa, Satoshi Yamada, Yorimitsu Koshikawa, Hiroshi Nakase, Hiroshi Seno.
    • Organizer
      The 4th Annual Meeting of Asian Organization for Crohn's and Colitis
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2016-07-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 潰瘍性大腸炎におけるEpstein-Barr Virusについての検討2016

    • Author(s)
      山田 聡, 松浦 稔, 本澤 有介, 南 尚希, 越川 頼光, 仲瀬 裕志.
    • Organizer
      第102回 日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2016-04-22
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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