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Pathophysiological role of regulatory oligosaccharides in inflammatory bowel disease

Research Project

Project/Area Number 25860535
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

Shinzaki Shinichiro  大阪大学, 医学(系)研究科(研究院), 助教 (60546860)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords制御性糖鎖 / 炎症性腸疾患 / 腸管免疫 / T細胞 / マクロファージ / GnT-V / FUT8 / 糖鎖
Outline of Final Research Achievements

In the present study we focused on the oligosaccharides on immune cells of patients with inflammatory bowel disease, and investigated the pathophysiological role of immunoregulatory oligosaccharides for colitis. We revealed that overexpression of N-Acetylglucosaminyltransferase V (GnT-V) exacerbated murine experimental colitis by inducing macrophage dysfunction. We also found using α1-6 fucosyltransferase (FUT8) deficient mice that core fucosylation of T-cell receptor is required for T-cell signaling and production of inflammatory cytokines and induction of colitis in mice. These results suggest the possibility of regulating colitis by oligosaccharides.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (32 results)

All 2016 2015 2014 2013

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis.2016

    • Author(s)
      Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
    • Journal Title

      J Gastroenterol

      Volume: 51 Issue: 4 Pages: 357-69

    • DOI

      10.1007/s00535-015-1112-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of aberrant IgG glycosylation in the pathogenesis of inflammatory bowel disease.2016

    • Author(s)
      Miyoshi E, Shinzaki S, Fujii H, Iijima H, Kamada Y, Takehara T.
    • Journal Title

      Proteomics Clinical Applications

      Volume: 未定 Issue: 4 Pages: 384-390

    • DOI

      10.1002/prca.201500089

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Acetylglucosaminyltransferase V exacerbates murine colitis with macrophage dysfunction and enhances colitic tumorigenesis.2016

    • Author(s)
      Shinzaki S, Ishii M, Fujii H, Iijima H, Wakamatsu K, Kawai S, Shiraishi E, Hiyama S, Inoue T, Hayashi Y, Kuwahara R, Takamatsu S, Kamada Y, Morii E, Tsujii M, Takehara T, Miyoshi E.
    • Journal Title

      J Gastroenterol.

      Volume: 51 Issue: 4 Pages: 357-369

    • DOI

      10.1007/s00535-015-1119-3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Core Fucosylation on T cells, Required for Activation of T-cell Receptor Signaling and Induction of Colitis in Mice, is Increased in Patients with Inflammatory Bowel Disease.2016

    • Author(s)
      Fujii H, Shinzaki S, Iijima H, Wakamatsu K, Iwamoto C, Sobajima T, Kuwahara R, Hiyama S, Hayashi Y, Takamatsu S, Uozumi N, Kamada Y, Tsujii M, Taniguchi N, Takehara T, Miyoshi E
    • Journal Title

      Gastroenterology

      Volume: 未定 Issue: 7 Pages: 00297-3

    • DOI

      10.1053/j.gastro.2016.03.002

    • NAID

      40021255019

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinico-Pathological Significance of Leucine-Rich Alpha-2-Glycoprotein-1 in Sera of Patients with Pancreatic Cancer2015

    • Author(s)
      Furukawa K, Kawamoto K, Eguchi H, Tanemura M, Tomimaru Y, Akita H, Hama N, Wada H, Kobayashi S, Nonaka Y, Takamatsu S, Shinzaki S, Kumada T, Satomura S, Ito T, Serada S, Naka T, Mori M, Doki Y,Miyoshi E, Nagano H.
    • Journal Title

      Pancreas.

      Volume: 44(1) Pages: 93-98

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum fucosylated haptoglobin in chronic liver diseases as a potential biomarker of hepatocellular carcinoma development.2015

    • Author(s)
      Kamada Y*, Asazawa H* (equally contributed), Takeda Y, Takamatsu S, Shinzaki S, Kim Y, Nezu R, Kuzushita N, Mita E, Kat M, Miyoshi E.
    • Journal Title

      Clin Chem Lab Med

      Volume: 53 Issue: 1 Pages: 95-102

    • DOI

      10.1515/cclm-2014-0427

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 5FU resistance abrogates the amplified cytotoxic effects induced by inhibiting checkpoint kinase 1 in p53‑mutated colon cancer cells.2015

    • Author(s)
      Akasaka T, Tsujii M, Kondo J, Hayashi Y, Ying J, Lu Y, Kato M, Yamada T, Yamamoto S, Inoue T, Tsujii Y, Maekawa A, Fujinaga T, Shiraishi E, Hiyama S, Inoue T, Shinzaki S, Watabe K, Nishida T, Iijima H, Takehara T.
    • Journal Title

      Int J Oncol.

      Volume: 46 Issue: 1 Pages: 63-70

    • DOI

      10.3892/ijo.2014.2693

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] N-Acetylglucosaminyltransferase V exacerbates concanavalin A‑induced hepatitis in mice.2015

    • Author(s)
      Kamada Y, Sato M, Kida S, Akita M, Mizutani K, Fujii H, Sobajima T, Yoshida Y, Shinzaki S, Takamatsu S, Takehara T, Miyoshi E.
    • Journal Title

      Mol Med Rep.

      Volume: 5 Issue: 5 Pages: 3573-84

    • DOI

      10.3892/mmr.2015.3168

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Twin studies on the effect of genetic factors on serum agalactosyl immunoglobulin G levels2014

    • Author(s)
      Azuma K, Shinzaki S, Asazawa H,Kuroki e, Miyosi E, Hayakawa k, et al.
    • Journal Title

      Biomedical Reports

      Volume: 2 Issue: 2 Pages: 21-26

    • DOI

      10.3892/br.2014.216

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Esophageal adenocarcinoma with white opaque substance observed by magnifying endoscopy with narrow band imaging.2014

    • Author(s)
      Yoshii S, Kato M, Honma K, Fujinaga T, Tsujii Y, Maekawa A, Inoue T, Hayashi Y, Akasaka T, Shinzaki S, Nishida T, Iijima H, Tsujii M, Morii E, Takehara T.
    • Journal Title

      Dig Endosc.

      Volume: 27 Issue: 3 Pages: 392-396

    • DOI

      10.1111/den.12331

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Esophageal early basaloid squamous carcinoma with unusual narrowband imaging magnified endoscopy findings.2014

    • Author(s)
      Kai Y, Kato M, Hayashi Y, Akasaka T, Shinzaki S, Nishida T, Tsujii M, Morii E, Takehara T.
    • Journal Title

      World J Gastroenterol.

      Volume: 20 Issue: 35 Pages: 12673-12677

    • DOI

      10.3748/wjg.v20.i35.12673

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peyer's Patches Play a Protective Role in Nonsteroidal Anti-inflammatory Drug-induced Enteropathy in Mice.2014

    • Author(s)
      Hiyama S, Iijima H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Kato M, Hayashi Y, Nishida T, Fujii H, Mukai A, Shibata N, Sato S, Kiyono H, Gotoh K, Motooka D, Nakamura S, Iida T, Tsujii M, Takehara T.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: 印刷中

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of anergy-related ubiquitin E3 ligase, GRAIL, in murine models of colitis and patients with Crohn's disease.2014

    • Author(s)
      Mukai A, Iijima H, Hiyama S, Fujii H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Hayashi Y, Kondo J, Mizushima T, Kanto T, Egawa S, Nishida T, Tsujii M, Takehara T.
    • Journal Title

      J Gastroenterol.

      Volume: 印刷中

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features of post-polypectomy bleeding associated with heparin bridge therapy.2014

    • Author(s)
      Inoue T, Nishida T, Maekawa A, Tsujii Y, Akasaka T, Kato M, Hayashi Y, Yamamoto S, Kondo J, Yamada T, Shinzaki S, Iijima H, Tsujii M, Takehara T.
    • Journal Title

      Dig Endosc.

      Volume: 26 Issue: 2 Pages: 243-249

    • DOI

      10.1111/den.12123

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amelioration of Small Bowel Injury by Switching from Nonselective Nonsteroidal Anti-Inflammatory Drugs to Celecoxib in Rheumatoid Arthritis Patients: A Pilot Study2013

    • Author(s)
      Inoue, T., Iijima, H., Arimitsu, J., Hagihara, K., Kawai, S., Shiraishi, E., Hiyama, S., Mukai, A., Shinzaki, S., Nishida, T., Ogata, A., Tsujii, M., Takehara, T.
    • Journal Title

      Digestion

      Volume: 89 Issue: 2 Pages: 124-132

    • DOI

      10.1159/000357229

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis.2013

    • Author(s)
      Nakayama K, Moriwaki K, Miyoshi E,et.al.
    • Journal Title

      PLoS One

      Volume: 8(7) Issue: 7 Pages: e70298-e70298

    • DOI

      10.1371/journal.pone.0070298

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease2013

    • Author(s)
      Hiyama, S., Iijima, H., Shinzaki, S., Mukai, A., Inoue, T., Shiraishi, E., Kawai, S., Yamada, T., Nishida, T., Tsujii, M., Takehara, T.
    • Journal Title

      Digestion

      Volume: 87 Issue: 4 Pages: 269-80

    • DOI

      10.1159/000349953

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease.2013

    • Author(s)
      Shinzaki S, 他13名, Naka T, Plevy S E, Takehara T, Miyoshi E.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: 19(2) Issue: 2 Pages: 321-31

    • DOI

      10.1097/mib.0b013e318280eade

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] マクロファージにおけるコアフコースはのTLR4シグナルを制御するにおけるコアフコースの関与2015

    • Author(s)
      若松可奈、藤井宏修、高松真二、鎌田佳宏、新崎信一郎、飯島英樹、鎌田佳宏、高松真二、竹原徹郎、三善英知
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腸炎関連性発癌におけるコアフコースの関与2015

    • Author(s)
      藤井宏修、新崎信一郎、飯島英樹、若松可奈、高松真ニ、鎌田佳宏、辻井正彦、竹原徹郎、三善英知
    • Organizer
      第74回日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新崎信一郎、飯島英樹、藤井宏修、 若松可奈、竹原徹郎、三善英知2015

    • Author(s)
      糖鎖変化が炎症性腸疾患の 病態に及ぼす影響と バイオマーカーとしての可能性
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学・安田記念講堂
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Core fucosylation regulates T-cell activation and ameliorates murine colitis2015

    • Author(s)
      Hironobu Fujii, Shinichiro Shinzaki, Hideki Iijima, Kana Wakamatsu, Chizuru Iwamoto, Shinji Takamatsu, Yoshihiro Kamada, Masahiko Tsujii, Tetsuo Takehara, Eiji Miyoshi
    • Organizer
      Digestive Disease Week 2015
    • Place of Presentation
      アメリカ・ワシントンDC
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn’s disease2015

    • Author(s)
      Manabu Araki, Shinichiro Shinzaki, Hideki Iijima, Toshio Yamaguchi, Shoichiro Kawai, Satoshi Hiyama, Takahiro Inoue, Yoshito Hayashi, Kenji Watabe, Masahiko Tsujii, and Tetsuo Takehara
    • Organizer
      10th congress of European Crohn's and Colitis Organisation
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2015-02-18 – 2015-02-21
    • Related Report
      2014 Research-status Report
  • [Presentation] フコシル化の低下は炎症性腸疾患における免疫抑制シグナルを増強する2014

    • Author(s)
      若松 可奈, 藤井 宏修, 新崎 信一郎, 飯島 英樹, 岩本 ちづる, 片岡 直也, 鎌田 佳宏, 竹原 徹郎, 三善 英知
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Importance of early endoscopic surveillance for postoperative Crohn’s disease patients2014

    • Author(s)
      Shinichiro Shinzaki, Hideki Iijima, Satoshi Hiyama, Junichi Nishimura, Tsunekazu Mizushima, Masahiko Tsujii, Tetsuo Takehara
    • Organizer
      Japan Digestive Disease Week 2014
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 炎症性腸疾患バイオマーカーとしてのLeucine-rich alpha-2 glycoprotein (LRG)の可能性2014

    • Author(s)
      新崎信一郎、飯島英樹、松岡克善、武下達矢、世良田聡、辻井正彦、金井隆典、竹原徹郎、仲哲治
    • Organizer
      第51回日本消化器免疫学会総会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] N-Acetylglucosaminyltransferase V (GnT-V) exacerbates murine experimental colitis with macrophage dysfunction and enhances colitis-associated tumorigenesis2014

    • Author(s)
      Shinichiro Shinzaki, Hideki Iijima, Hironobu Fujii, Shoichiro Kawai, Manabu Araki, Satoshi Hiyama, Yoshito Hayashi, Kenji Watabe, Masahiko Tsujii, Eiji Miyoshi, and Tetsuo Takehara
    • Organizer
      The 2nd annual meeting of Asian Organization of Crohn's and Colitis
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Deficiency of fucosylation as a protective role for intestinal inflammation2013

    • Author(s)
      Hironobu Fujii, Shinichiro Shinzaki, Mayuko Ishii, Yoshihiro Kamada, Hideki Iijima, Masahiko Tsujii, Tetsuo Takehara, and Eiji Miyoshi
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      オーランド(アメリカ)
    • Related Report
      2013 Research-status Report
  • [Presentation] Postoperative combination of nutritional therapy and infliximab for sustained remission of adult Crohn’s disease2013

    • Author(s)
      Shinichiro Shinzaki, Hideki Iijima, Tsunekazu Mizushima, Kiyokazu Nakajima, Shoichiro Kawai, Eri Shiraishi, Satoshi Hiyama, Akira Mukai, Takahiro Inoue, Takuya Yamada, Tsutomu Nishida, Masahiko Tsujii, Tetsuo Takehara
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      オーランド(アメリカ)
    • Related Report
      2013 Research-status Report
  • [Presentation] Altered oligosaccharide structures reduce colitis induction in mice defective in beta-1,4-Galactosyltransferase2013

    • Author(s)
      Shinichiro Shinzaki, Hideki Iijima, Hironobu Fujii, Shoichiro Kawai, Eri Shiraishi, Satoshi Hiyama, Akira Mukai, Takahiro Inoue, Masahiko Tsujii, Eiji Miyoshi and Tetsuo Takehara
    • Organizer
      1st Annual Meeting of Asian Organization for Crohn's & Colitis
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Lectin-based immunoassay for "Agalactosyl IgG" as the biomarker for Crohn's disease2013

    • Author(s)
      Shinichiro Shinzaki, Hideki Iijima, Shoichiro Kawai, Eri Shiraishi, Satoshi Hiyama, Akira Mukai, Takahiro Inoue, Tsutomu Nishida, Scott E. Plevy, Masahiko Tsujii, Eiji Miyoshi and Tetsuo Takehara
    • Organizer
      1st Annual Meeting of Asian Organization for Crohn's & Colitis
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] クローン病術後の栄養療法・生物学的製剤併用の有用性2013

    • Author(s)
      新崎信一郎、飯島英樹、竹原徹郎
    • Organizer
      第21回日本消化器病学会週間
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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