Enteric environment analysis in intestinal inflammation and colitis-associated cancer based on glycomic approach

• Project/Area Number: 16K09310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Shinzaki Shinichiro 大阪大学, 医学系研究科, 講師 (60546860)
• Co-Investigator(Kenkyū-buntansha): 日山 智史 大阪大学, 医学系研究科, 寄附講座助教 (10735335) ; 林 義人 大阪大学, 医学系研究科, 助教 (80647123) ; 飯島 英樹 大阪大学, 医学系研究科, 准教授 (90444520)
• Research Collaborator: Iwatani Shuko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 糖鎖 / ガレクチン / マクロファージ / 炎症性腸疾患 / IL-10 / ポリラクトサミン / 腸内細菌 / 内科

Outline of Final Research Achievements

In patients with ulcerative colitis, the expression of Galectin-1, found by our previous oligosaccharide analyses, was significantly decreased in inflamed colonic mucosa than in non-inflamed mucosa. When murine macrophages were stimulated with Galectin-1, the expression of interleukin-10 was significantly upregulated compared with those unstimulated. Murine colitis model was significantly ameliorated in mice stimulated with Galectin-1-treated macrophages than mice stimulated with vehicle-treated ones. These results indicate that Galectin-1 has a pivotal role in ameliorating murine colitis by affecting macrophage function.

Academic Significance and Societal Importance of the Research Achievements

本研究において、糖鎖を認識するレクチンの一種である、Galectin-1に腸炎抑制作用があることが示されるとともに、マクロファージを介した抗炎症性サイトカインであるインターロイキン（IL）-10が腸炎抑制に関わっていることが明らかとなった。また、炎症性腸疾患患者の腸管炎症部においてGalectin-1の発現が低下していた。これらの成果は、糖鎖を介した炎症性腸疾患の病態解明の一助となるとともに、Galectin-1が糖鎖を介して炎症性腸疾患治療の標的となる可能性を示すものと考えられる。

Research Products

• [Journal Article] Core fucose is essential glycosylation for CD14-dependent Toll-like receptor 4 and Toll-like receptor 2 signaling in macrophages (2018)
  • Author(s): Nakayama K, Wakamatsu K, Fujii H, Shinzaki S, Takamatsu S, Kitazume S, Kamada Y, Takehara T, Taniguchi N, Miyoshi E
  • Journal Title: J Biochem Volume: ー Issue: 3 Pages: 227-237
  • DOI: 10.1093/jb/mvy098
  • NAID: 40021845862
  • Peer Reviewed
• [Journal Article] Tissue drug concentrations of anti-tumor necrosis factor agents are associated with the long-term outcome of patients with Crohn's disease. (2017)
  • Author(s): Yoshihara T, Shinzaki S, Kawai S, Fujii H, Iwatani S, Yamaguchi T, Araki M, Hiyama S, Inoue T, Hayashi Y, Watabe K, Iijima H, Takehara T.
  • Journal Title: Inflamm Bowel Dis. Volume: 23(12) Issue: 12 Pages: 2172-2179
  • DOI: 10.1097/mib.0000000000001260
  • Peer Reviewed
• [Journal Article] A novel pathogenesis of inflammatory bowel disease from the perspective of glyco-immunology. (2017)
  • Author(s): Shinzaki S, Iijima H, Fujii H, Kamada Y, Naka T, Takehara T, Miyoshi E.
  • Journal Title: J Biochem. Volume: 印刷中 Issue: 5 Pages: 409-415
  • DOI: 10.1093/jb/mvx010
  • Peer Reviewed
• [Journal Article] Age at onset is associated with the seasonal pattern of onset and exacerbation in inflammatory bowel disease (2017)
  • Author(s): Araki, M, Shinzaki, S., Yamada, T., Arimitsu S., Komori, M., Shibukawa, N., Mukai A., Nakajima, S., Kinoshita, K., Kitamura, S., Murayama, Y., Ogawa H., Yasunaga Y, Oshita, M., Fukui, H., Masuda E., Tsujii, M., Hiyama, S., Inoue, T., Iijima, H., Takehara, T.
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 11 Pages: 1149-1157
  • DOI: 10.1007/s00535-017-1313-6
  • Peer Reviewed
• [Journal Article] Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis (2017)
  • Author(s): Shinzaki, S., Matsuoka, K., Iijima, H., Mizuno, S., Serada, S., Fujimoto, M., Arai, N. Koyama, N., Morii, E., Watanabe, M., Hibi, T., Kanai, T., Takehara, T., Naka, T.
  • Journal Title: Journal of Crohn's and Colitis Volume: 11(1) Issue: 1 Pages: 84-91
  • DOI: 10.1093/ecco-jcc/jjw132
  • Peer Reviewed
• [Journal Article] Indigo Naturalis ameliorates murine dextran sodium sulfate-induced colitis via aryl hydrocarbon receptor activation. (2017)
  • Author(s): Kawai S, Iijima H, Shinzaki S, Hiyama S, Yamaguchi T, Araki M, Iwatani S, Shiraishi E, Mukai A, Inoue T, Hayashi Y, Tsujii M, Motooka D, Nakamura S, Iida T, Takehara T.
  • Journal Title: J Gastroenterol. Volume: in press
  • Peer Reviewed
• [Journal Article] Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly. (2016)
  • Author(s): Kamada Y, Kida S, Hirano KI, Yamaguchi S, Suzuki A, Hashimoto C, Kimura A, Sato M, Fujii H, Sobajima T, Yamamoto A, Ebisutani Y, Takamatsu S, Shinzaki S, Yoshida Y, Yamada M, Nagasaka H, Takehara T, Miyoshi E.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 311 Issue: 5 Pages: G859-G868
  • DOI: 10.1152/ajpgi.00231.2016
  • Peer Reviewed / Acknowledgement Compliant
• [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
• [Presentation] Oligosaccharide-dependent anti-inflammatory role of galectin-1 in inflammatory bowel disease (2018)
  • Author(s): Shuko Iwatani, Shinichiro Shinzaki, Hideki Iijima, Yuriko Otake, Mizuki Tani, Takeo Yoshihara, Toshio Yamaguchi, Shoichiro Kawai, Takahiro Inoue, Yoshito Hayashi, and Tetsuo Takehara
  • Organizer: Digestive Disease Week 2018
  • Int'l Joint Research
• [Presentation] IBD患者のLipidomics解析 (2018)
  • Author(s): 岩谷修子、飯島英樹、天野孝広、大竹由利子、谷瑞季、良原丈夫、辻井芳樹、井上隆弘、林義人、新﨑信一郎、林昭夫、藤田節子、竹原徹郎
  • Organizer: 第55回日本消化器免疫学会総会
• [Presentation] IBD患者における増悪に関与する腸内細菌叢の検討 (2018)
  • Author(s): 谷 瑞季、新崎 信一郎、天野 孝広、大竹 由利子、良原 丈夫、岩谷 修子、荒木 学、辻井 芳樹、林 義人、井上 隆弘、飯島 英樹、竹原 徹郎
  • Organizer: 第9回日本炎症性腸疾患学会
• [Presentation] Dynamic regulation of T cell receptors via core fucosylation is a novel mechanism involved in the onset of inflammatory bowel disease (2016)
  • Author(s): Shinichiro Shinzaki, Hironobu Fujii, Hideki Iijima, Satoshi Hiyama, Yoshito Hayashi, Shinji Takamatsu, Yoshihiro Kamada, Masahiko Tsujii, Tetsuo Takehara, Eiji Miyoshi.
  • Organizer: The 4th annual meeting of Asian Organization for Crohn's and Colitis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2016-07-07
  • Int'l Joint Research