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The effect of Wnt5a derived peptide to reduce intestinal inflammation

Research Project

Project/Area Number 18K06224
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Uchiyama Kazuhiko  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50298428)

Co-Investigator(Kenkyū-buntansha) 内藤 裕二  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00305575)
高木 智久  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70405257)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsWnt5a / 炎症性腸疾患 / サイトカイン / ペプチド / 抗炎症 / 潰瘍性大腸炎 / 粘膜 / DSS腸炎 / 再燃 / IBD / 炎症性サイトカイン / peptide
Outline of Final Research Achievements

In this study, we investigated the anti-inflammatory effects of Wnt5a peptide on colonic inflammation.
In the mouse DSS colitis model, intraperitoneal administration of Wnt5a peptide suppressed cytokine expression in the colonic mucosa and intestinal injury. In addition, Wnt5a mRNA expression in the colonic mucosa was examined in 51 patients with ulcerative colitis in remission. The results showed that Wnt5a mRNA expression in the mucosa was significantly lower in patients who relapsed in the subsequent clinical course. In addition, Wnt5a mRNA expression was inversely correlated with inflammatory cytokine expression in the colonic mucosa.
These results indicate that activation of the Wnt5a pathway with Wnt5a peptide has anti-inflammatory effects in the intestinal mucosa.

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎患者は原因不明の炎症性疾患であり、本邦で患者数は増加している。現在、様々な作用機序の薬剤が臨床応用されているが、それでも病勢の制御が困難で手術に至ってしまうケースも少なからず存在する。
これまで、大腸粘膜の炎症におけるWnt5aの役割は不明であったが、本研究を通してWnt5aの抗炎症作用が明らかとなった。これは潰瘍性大腸炎患者の臨床経過においても同様の結果であり、基礎的な研究と臨床経過とが一貫する結果であった。
今回Wnt5aペプチドが大腸粘膜における抗炎症作用を有していることが分かり、将来的な創薬も含め潰瘍性大腸炎の病態解明および新規治療の可能性を示唆する結果であった。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 3 results) Presentation (1 results) Funded Workshop (2 results)

  • [Journal Article] Identification of colorectal neoplasia by using serum bile acid profile2021

    • Author(s)
      Uchiyama Kazuhiko、Naito Yuji、Yagi Nobuaki、Mizushima Katsura、Higashimura Yasuki、Hirai Yasuko、Dohi Osamu、Okayama Tetsuya、Yoshida Naohisa、Katada Kazuhiro、Kamada Kazuhiro、Ishikawa Takeshi、Takagi Tomohisa、Konishi Hideyuki、Kuriu Yoshiaki、Nakanishi Masayoshi、Otsuji Eigo、Honda Akira、Itoh Yoshito
    • Journal Title

      Biomarkers

      Volume: - Issue: 5 Pages: 1-6

    • DOI

      10.1080/1354750x.2021.1917663

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis2021

    • Author(s)
      Uchiyama Kazuhiko、Takagi Tomohisa、Mizushima Katsura、Kajiwara-Kubota Mariko、Kashiwagi Saori、Toyokawa Yuki、Tanaka Makoto、Hotta Yuma、Kamada Kazuhiro、Ishikawa Takeshi、Konishi Hideyuki、Kishimoto Mitsuo、Naito Yuji、Itoh Yoshito
    • Journal Title

      BMC Gastroenterology

      Volume: 21 Issue: 1

    • DOI

      10.1186/s12876-021-01709-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic Potential of Astaxanthin in Diabetic Kidney Disease2021

    • Author(s)
      Naito Yuji、Uchiyama Kazuhiko、Handa Osamu、Aoi Wataru
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 1261 Pages: 239-248

    • DOI

      10.1007/978-981-15-7360-6_22

    • ISBN
      9789811573590, 9789811573606
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low serum albumin at admission is a predictor of early colectomy in patients with moderate to severe ulcerative colitis2021

    • Author(s)
      Tanaka Makoto、Takagi Tomohisa、Naito Yuji、Uchiyama Kazuhiko、Hotta Yuma、Toyokawa Yuki、Kashiwagi Saori、Kamada Kazuhiro、Ishikawa Takeshi、Yasuda Hiroaki、Konishi Hideyuki、Itoh Yoshito
    • Journal Title

      JGH Open

      Volume: 5 Issue: 3 Pages: 377-381

    • DOI

      10.1002/jgh3.12506

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The efficacy of linked color imaging for the endoscopic diagnosis of mucosal healing in quiescent ulcerative colitis2021

    • Author(s)
      Takagi Tomohisa、Uchiyama Kazuhiko、Kajiwara‐Kubota Mariko、Kashiwagi Saori、Toyokawa Yuki、Hotta Yuma、Tanaka Makoto、Inoue Ken、Dohi Osamu、Yoshida Naohisa、Kamada Kazuhiro、Ishikawa Takeshi、Konishi Hideyuki、Kishimoto Mitsuo、Yagi Nobuaki、Naito Yuji、Itoh Yoshito
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 12 Issue: 9 Pages: 2448-2454

    • DOI

      10.1111/jgh.15489

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rectal administration of carbon monoxide inhibits the development of intestinal inflammation and promotes intestinal wound healing via the activation of the Rho-kinase pathway in rats.2021

    • Author(s)
      Takagi T, Naito Y, Higashimura Y, Uchiyama K, Okayama T, Mizushima K, Katada K, Kamada K, Ishikawa T, Itoh Y.
    • Journal Title

      Nitric Oxide.

      Volume: 107 Pages: 19-30

    • DOI

      10.1016/j.niox.2020.12.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the Gut Microbiota are Associated with Hypertension, Hyperlipidemia, and Type 2 Diabetes Mellitus in Japanese Subjects2020

    • Author(s)
      Takagi Tomohisa、Naito Yuji、Kashiwagi Saori、Uchiyama Kazuhiko、Mizushima Katsura、Kamada Kazuhiro、Ishikawa Takeshi、Inoue Ryo、Okuda Kayo、Tsujimoto Yoshimasa、Ohnogi Hiromu、Itoh Yoshito
    • Journal Title

      Nutrients

      Volume: 12 Issue: 10 Pages: 2996-2996

    • DOI

      10.3390/nu12102996

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trans-unsaturated fatty acid activates NLRP3 inflammasome in macrophages and exacerbates intestinal inflammation in mice2020

    • Author(s)
      Higashimura Yasuki、Tanaka Yumiko、Takagi Tomohisa、Uchiyama Kazuhiko、Mizushima Katsura、Niki Etsuo、Naito Yuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 2 Pages: 243-250

    • DOI

      10.1016/j.bbrc.2020.06.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Promotion of wound healing by acetate in murine colonic epithelial cell via c‐Jun N‐terminal kinase activation2020

    • Author(s)
      Nakano Takahiro、Uchiyama Kazuhiko、Ushiroda Chihiro、Kashiwagi Saori、Toyokawa Yuki、Mizushima Katsura、Inoue Ken、Dohi Osamu、Okayama Tetsuya、Yoshida Naohisa、Katada Kazuhiro、Kamada Kazuhiro、Handa Osamu、Ishikawa Takeshi、Takagi Tomohisa、Konishi Hideyuki、Naito Yuji、Itoh Yoshito
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 35 Issue: 7 Pages: 1171-1179

    • DOI

      10.1111/jgh.14987

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis in Mice2019

    • Author(s)
      Higashimura Yasuki、Takagi Tomohisa、Naito Yuji、Uchiyama Kazuhiko、Mizushima Katsura、Tanaka Makoto、Hamaguchi Masahide、Itoh Yoshito
    • Journal Title

      Journal of Crohn's and Colitis

      Volume: - Issue: 6 Pages: 856-866

    • DOI

      10.1093/ecco-jcc/jjz193

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Green tea polyphenol (epigallocatechin-3-gallate) improves gut dysbiosis and serum bile acids dysregulation in high-fat diet-fed mice2019

    • Author(s)
      Ushiroda Chihiro、Naito Yuji、Takagi Tomohisa、Uchiyama Kazuhiko、Mizushima Katsura、Higashimura Yasuki、Yasukawa Zenta、Okubo Tsutomu、Inoue Ryo、Honda Akira、Matsuzaki Yasushi、Itoh Yoshito
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 65 Issue: 1 Pages: 34-46

    • DOI

      10.3164/jcbn.18-116

    • NAID

      130007672107

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal microbiome as a novel therapeutic target for local and systemic inflammation2019

    • Author(s)
      Uchiyama Kazuhiko、Naito Yuji、Takagi Tomohisa
    • Journal Title

      Pharmacology & Therapeutics

      Volume: 199 Pages: 164-172

    • DOI

      10.1016/j.pharmthera.2019.03.006

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mucosa-Associated Microbiota in the Gastrointestinal Tract of Healthy Japanese Subjects2019

    • Author(s)
      Kashiwagi Saori、Naito Yuji、Inoue Ryo、Takagi Tomohisa、Nakano Takahiro、Inada Yutaka、Fukui Akifumi、Katada Kazuhiro、Mizushima Katsura、Kamada Kazuhiro、Uchiyama Kazuhiko、Handa Osamu、Ishikawa Takeshi、Itoh Yoshito
    • Journal Title

      Digestion

      Volume: 101 Issue: 2 Pages: 107-120

    • DOI

      10.1159/000496102

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevated ER stress exacerbates dextran sulfate sodium-induced colitis in PRDX4-knockout mice2019

    • Author(s)
      Takagi T, Homma T, Fujii J, Shirasawa N, Yoriki H, Hotta Y, Higashimura Y, Mizushima K, Hirai Y, Katada K, Uchiyama K, Naito Y, Itoh Y.
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 134 Pages: 153-164

    • DOI

      10.1016/j.freeradbiomed.2018.12.024

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selected reaction monitoring for colorectal cancer diagnosis using a set of five serum peptides identified by BLOTCHIP((R))-MS analysis2018

    • Author(s)
      Uchiyama, K. Naito, Y. Yagi, N. Mizushima, K. Higashimura, Y. Hirai, Y. Dohi, O. Okayama, T. Yoshida, N. Katada, K. Kamada, K. Handa, O. Ishikawa, T. Takagi, T. Konishi, H. Nonaka, D. Asada, K. Lee, L. J. Tanaka, K. Kuriu, Y. Nakanishi, M. Otsuji, E. Itoh, Y.
    • Journal Title

      J Gastroenterol

      Volume: 印刷中 Issue: 11 Pages: 1179-1185

    • DOI

      10.1007/s00535-018-1448-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Proteolytic bioactive form of Wnt5a is related to the pathogenesis of IBD in view of mucosal healing and anti-inflammation2018

    • Author(s)
      Uchiyama Kazuhiko, Tomohisa Takagi, Yuji Naito
    • Organizer
      JDDW 2018
    • Related Report
      2018 Research-status Report
  • [Funded Workshop] 14th Congress of European Crohn's and Colitis Organisation(ECCO)2019

    • Related Report
      2018 Research-status Report
  • [Funded Workshop] Digestive Disease Week(DDW)20182018

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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