Pathophysiological role of regulatory oligosaccharides in inflammatory bowel disease

• Project/Area Number: 25860535
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Clinico-Pathological Significance of Leucine-Rich Alpha-2-Glycoprotein-1 in Sera of Patients with Pancreatic Cancer (2015)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Twin studies on the effect of genetic factors on serum agalactosyl immunoglobulin G levels (2014)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 Study (2013)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease (2013)
  • 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
  • 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
  • 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
• [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
• [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
  • Invited
• [Presentation] Core fucosylation regulates T-cell activation and ameliorates murine colitis (2015)
  • 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
  • Int'l Joint Research
• [Presentation] Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn’s disease (2015)
  • 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
• [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
• [Presentation] Importance of early endoscopic surveillance for postoperative Crohn’s disease patients (2014)
  • 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
• [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
• [Presentation] N-Acetylglucosaminyltransferase V (GnT-V) exacerbates murine experimental colitis with macrophage dysfunction and enhances colitis-associated tumorigenesis (2014)
  • 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
• [Presentation] Deficiency of fucosylation as a protective role for intestinal inflammation (2013)
  • 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）
• [Presentation] Postoperative combination of nutritional therapy and infliximab for sustained remission of adult Crohn’s disease (2013)
  • 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）
• [Presentation] Altered oligosaccharide structures reduce colitis induction in mice defective in beta-1,4-Galactosyltransferase (2013)
  • 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
• [Presentation] Lectin-based immunoassay for "Agalactosyl IgG" as the biomarker for Crohn's disease (2013)
  • 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
• [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