• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis for the development of novel therapy against inflammatory bowel diseases based on the normalization of gut microbiota balance

Research Project

Project/Area Number 16H05086
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionChiba University

Principal Investigator

Kawashima Hiroto  千葉大学, 大学院薬学研究院, 教授 (50260336)

Co-Investigator(Kenkyū-buntansha) 平川 城太朗  千葉大学, 大学院薬学研究院, 助教 (30609160)
Research Collaborator Komatsu Masaaki  
Katayama Takane  
Kobayashi Motohiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsオートファジー / 腸内細菌 / 抗菌ペプチド / ムチン / 大腸炎 / 免疫学
Outline of Final Research Achievements

In this study, we found that colonic epithelium-specific autophagy-related gene Atg7-conditional knockout (cKO) mice showed exacerbated dextran sulfate sodium (DSS)-induced colitis compared with wild-type mice in relation to massive infiltration of bacteria into the colon. In the cKO mice, expression of specific antimicrobial peptides was significantly reduced, and marked changes in gut microbiota were observed. Furthermore, in cKO mice, the secretion of mucins that are involved in the protection of colonic mucus and inflammation was significantly reduced. These results suggest that autophagy of the colonic epithelium contributes to the regulation of normal intestinal bacterial balance and defense against inflammation via antimicrobial peptide and mucin production.

Academic Significance and Societal Importance of the Research Achievements

大腸上皮細胞のオートファジーは、抗菌ペプチドの発現、正常な腸内細菌叢の維持、およびムチン分泌を維持することで、大腸炎の防御に寄与することが示唆された。今後は、オートファジーの欠損によって産生低下する抗菌ペプチドが作用する菌種の同定やその作用機序の解明等により、腸内細菌バランスの正常化に基づく炎症性腸疾患治療法開発の分子基盤が確立することが期待される。

Report

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

    (43 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (34 results) (of which Int'l Joint Research: 6 results,  Invited: 7 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Academia Sinica(台湾)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Forced Expression of CXCL10 Prevents Liver Metastasis of Colon Carcinoma Cells by the Recruitment of Natural Killer Cells2019

    • Author(s)
      Kikuchi Norihito、Ye Jiabin、Hirakawa Jotaro、Kawashima Hiroto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 57-65

    • DOI

      10.1248/bpb.b18-00538

    • NAID

      130007542204

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Chaperone-mediated secretion switching from early to middle substrates in the type III secretion system encoded by Salmonella pathogenicity island 22019

    • Author(s)
      Takaya Akiko、Takeda Hikari、Tashiro Shogo、Kawashima Hiroto、Yamamoto Tomoko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 10 Pages: 3783-3793

    • DOI

      10.1074/jbc.ra118.005072

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 新規抗糖鎖モノクローナル抗体を用いたリンパ球体内動態の解析2018

    • Author(s)
      平川城太朗、川島博人
    • Journal Title

      生化学

      Volume: 90 Pages: 231-234

    • NAID

      40021617548

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches2018

    • Author(s)
      Uchida Tomomi、Ueta Hisashi、Xu Xue-Dong、Hirakawa Jotaro、Tahara Kazunori、Zhou Shu、Sawanobori Yasushi、Simmons Szandor、Kitazawa Yusuke、Kawashima Hiroto、Matsuno Kenjiro
    • Journal Title

      International Immunology

      Volume: 30 Issue: 1 Pages: 23-33

    • DOI

      10.1093/intimm/dxx072

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of MAdCAM-1-expressing high endothelial venule-like vessels in colitis induced in mice lacking sulfotransferases catalyzing L-selectin ligand biosynthesis.2018

    • Author(s)
      Low S, Hirakawa J, Hoshino H, Uchimura K, Kawashim H, Kobayashi M
    • Journal Title

      J Histochem Cytochem

      Volume: 1:22155417753363 Issue: 6 Pages: 415-425

    • DOI

      10.1369/0022155417753363

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma.2016

    • Author(s)
      Shulin L, Sakai Y., Hoshino H, Hirokawa M, Kawashima H, Higuchi K, Imamura Y, Kobayashi M
    • Journal Title

      Pathology

      Volume: 48 Issue: 7 Pages: 666-674

    • DOI

      10.1016/j.pathol.2016.08.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抗糖鎖抗体S1を用いた中枢神経系における硫酸化糖鎖の発現解析2019

    • Author(s)
      山﨑郁弥、泉水友洋、岩﨑藍花、大八木真浩、神谷映里、平川城太朗、川島博人
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気管支喘息モデルにおける抗シリアルルイスX糖鎖抗体の治療効果の検討2019

    • Author(s)
      熊偉、劉偉、松岡美紗、平川城太朗、川島博人
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ケモカインCXCL10の過剰発現によるNK細胞浸潤の誘導と大腸がん細胞の肝転移の抑制2019

    • Author(s)
      菊池紀仁、叶家斌、平川城太朗、川島博人
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Anti-sulfated-glycan monoclonal antibody S2 inhibits lymphocyte recruitment to nasal-associated lymphoid tissues and attenuates allergic rhinitis.2018

    • Author(s)
      Hirakawa J and Kawashima H
    • Organizer
      AAI Annual Meeting (IMMUNOLOGY 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 乳癌における高内皮細静脈の発現状況について2018

    • Author(s)
      中井克也、堀本義哉、荒川敦、齊藤光江、川島博人、入村達郎
    • Organizer
      第26回日本乳癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖鎖分子を標的とした新規アレルギー疾患治療抗体の開発2018

    • Author(s)
      平川城太朗、川島博人
    • Organizer
      第19回Pharmaco-Hematology symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗糖鎖抗体S1を用いた中枢神経系における硫酸化糖鎖の発現解析2018

    • Author(s)
      山崎郁弥、泉水友洋、岩崎藍花、大八木真浩、神谷映里、平川城太朗、川島博人
    • Organizer
      第37回 日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖と免疫2018

    • Author(s)
      川島博人
    • Organizer
      TIAナノバイオサマースクール
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 抗糖鎖抗体S1を用いた中枢神経系における硫酸化糖鎖の発現解析2018

    • Author(s)
      山崎郁弥、泉水友洋、岩崎藍花、大八木真浩、神谷映里、平川城太朗、川島博人
    • Organizer
      第91 回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規抗糖鎖モノクローナル抗体F2を用いた気管支喘息モデルの治療効果の検討2018

    • Author(s)
      熊偉、劉偉、松岡美紗、平川城太朗、川島博人
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ケモカインCXCL10による大腸がん細胞の肝転移の抑制2018

    • Author(s)
      菊池紀仁、葉家斌、平川城太朗、川島博人
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] L-セレクチンのリガンド糖鎖を標的とする抗糖鎖抗体の開発と医療応用への可能性2018

    • Author(s)
      川島博人
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] HEVにおける硫酸化ガラクトースを含む糖鎖の発現解析2018

    • Author(s)
      関根成隆、竹添智宏、西田匠吾、平川城太朗、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気管支喘息モデルにおける抗シアリルルイスX糖鎖抗体の治療効果の検討2018

    • Author(s)
      熊偉、劉偉、松岡美紗、平川城太朗、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗糖鎖抗体S1を用いた中枢神経系における硫酸化糖鎖の発現解析2018

    • Author(s)
      山崎郁弥、泉水友洋、岩崎藍花、大八木真浩、神谷映里、平川城太朗、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] リンパ球ホーミングにおける硫酸化糖鎖の機能解明2018

    • Author(s)
      川島博人
    • Organizer
      糖鎖免疫研究会Glyco-immunology 2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] フコシル化糖鎖sialyl Lewis Xの新規生合成経路の解析2018

    • Author(s)
      佐藤裕之、松浦寛明、小林純子、栂谷内晶、成松久、Kay-Hooi Khoo、川島博人
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスB細胞におけるフコシル化糖鎖抗原シアリルルイスXの発現解析2018

    • Author(s)
      竹添智宏、松村龍志、関根成隆、平川城太朗、川島博人
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗糖鎖モノクローナル抗体によるアレルギー性免疫応答の抑制2017

    • Author(s)
      平川城太朗、川島博人
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス卵管におけるフコシル化糖鎖sialyl Lewis Xの生合成経路の解析2017

    • Author(s)
      佐藤裕之、松浦寛明、小林純子、栂谷内晶、成松久、Kay-Hooi Khoo、川島博人
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Detection and functional characterization of sialyl Lewis X antigen in mice using novel anti-carbohydrate monoclonal antibodies.2017

    • Author(s)
      Matsumura R, Hirakawa J, Fukuda M, Imai Y and Kawashima H
    • Organizer
      24th International Symposium on Glycoconjugates (GLYCO XXIV)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of allergic rhinitis by anti-sulfated-glycan monoclonal antibodies.2017

    • Author(s)
      Hirakawa J and Kawashima H
    • Organizer
      24th International Symposium on Glycoconjugates (GLYCO XXIV),
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA chaperons, CspC and CspE regulate mRNAs induced in Salmonella surviving in macrophages after phagocytosis.2017

    • Author(s)
      Kimura N, Yamamoto T, Kawashima H, Takaya A
    • Organizer
      5th ASM Conference on Salmonella
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス卵管におけるフコシル化糖鎖sialyl Lewis Xの生合成経路の解析2017

    • Author(s)
      佐藤裕之、松浦寛明、小林純子、栂谷内晶、成松久、Kay-Hooi Khoo、川島博人
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスB細胞におけるフコシル化糖鎖抗原シアリルルイスXの発現解析2017

    • Author(s)
      竹添智宏、松村龍志、関根成隆、平川城太朗、川島博人
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス卵管におけるsialyl Lewis X生合成経路の解析2017

    • Author(s)
      佐藤裕之、松浦寛明、小林純子、栂谷内晶、成松久、Kay-Hooi Khoo、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中枢神経系における硫酸化糖鎖の発現解析2017

    • Author(s)
      泉水友洋、岩﨑藍花、大八木真浩、山﨑郁弥、平川城太朗、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスB細胞におけるフコシル化糖鎖抗原シアリルルイスXの発現解析2017

    • Author(s)
      竹添智宏、松村龍志、関根成隆、平川城太朗、川島博人
    • Organizer
      グローバルプロミネント研究基幹シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] リンパ球ホーミングにおける硫酸化糖鎖の機能解明:遺伝子欠損マウスを用いた解析2017

    • Author(s)
      川島博人
    • Organizer
      名城大学組換えDNA講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Detection and functional characterization of sialyl Lewis X antigen in mice using novel anti-carbohydrate monoclonal antibodies.2016

    • Author(s)
      川島博人
    • Organizer
      6th Charles Warren Workshop 2016
    • Place of Presentation
      北海道大学 (北海道札幌市)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of sulfated glycans in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses.2016

    • Author(s)
      川島博人
    • Organizer
      Glycoscience Japan-The Netherlands Joint Seminar 2016
    • Place of Presentation
      Leiden University (Leiden, the Netherlands)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リンパ球ホーミングにおける硫酸化糖鎖の役割2016

    • Author(s)
      川島博人
    • Organizer
      再生システムと疾患・癌エピゲノム公開シンポジウム
    • Place of Presentation
      千葉大学 (千葉市中央区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 硫酸化糖鎖の機能阻害に基づくアレルギー応答の制御2016

    • Author(s)
      川島博人
    • Organizer
      第60回日本薬学会関東支部大会
    • Place of Presentation
      東京大学 (東京都文京区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 抗糖鎖抗体の開発と利用2016

    • Author(s)
      川島博人
    • Organizer
      順天堂大学難病の診断と治療研究センター糖鎖創薬研究室開設記念シンポジウム
    • Place of Presentation
      順天堂大学 (東京都文京区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 未来を創るグライコサイエンス-我が国のロードマップ-2018

    • Author(s)
      川島博人(分担執筆)
    • Total Pages
      334
    • Publisher
      日本糖質科学コンソーシアム
    • Related Report
      2018 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院 免疫微生物学研究室

    • URL

      http://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-08-05  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi