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

Development of inflammatory bowel disease treatment by restoration of intestinal epithelial barrier functions

Research Project

Project/Area Number 26860078
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionOsaka University

Principal Investigator

Akihiro Watari  大阪大学, 薬学研究科(研究院), 助教 (80452465)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords上皮バリア機能制御 / 炎症性腸疾患治療法 / クローディン発現 / タイトジャンクション / 炎症性腸疾患 / クローディン / 上皮バリア / daunorubicin / rebeccamycin
Outline of Final Research Achievements

In this study, we identified daunorubicin and rebecamycin as novel claudin modulators, which can enhance tight junction (TJ) barrier function in intestinal cells. Daunorubicin and rebeccamycin stimulate ATM and ATR kinases in the nucleus, resulting in activation of the downstream molecule, Chk1. Activated Chk1 increases claudin-5 expression, and the product of claudin-5 transitions to TJ following enhanced TJ-barrier. Furthermore, we constituted claudin-2 reporter system, and identified novel claudin-2 modulators from chemical library. In the future, we will investigate therapeutic effect of multiple claudin modulators for an inflammatory bowel disease.

Report

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

    (21 results)

All 2016 2015 2014

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 6 results) Presentation (13 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Checkpoint Kinase 1 Activation Enhances Intestinal Epithelial Barrier Function via Regulation of Claudin-5 Expression2016

    • Author(s)
      Watari A., Hasegawa M., Yagi K., Kondoh M.
    • Journal Title

      PLoS One

      Volume: 11 (1) Issue: 1 Pages: e0145631-e0145631

    • DOI

      10.1371/journal.pone.0145631

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Claudin-1 Binder Enhances Epidermal Permeability in a Human Keratinocyte Model2015

    • Author(s)
      Nakajima M, Nagase S, Iida M, Takeda S, Yamashita M, Watari A, Shirasago Y, Fukasawa M, Takeda H, Sawasaki T, Yagi K, Kondoh M
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 354 Issue: 3 Pages: 440-447

    • DOI

      10.1124/jpet.115.225391

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-HCV effect of mycelia solid culture extracts of Lentinula edodes and low-molecular-weight lignin2015

    • Author(s)
      Matsuhisa K., Yamane S., Okamoto T., Watari A., Kondoh M., Matsuura Y., Yagi K.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 462(1) Issue: 1 Pages: 52-7

    • DOI

      10.1016/j.bbrc.2015.04.104

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C-terminal Clostridium perfringens enterotoxin-mediated antigen delivery for nasal pneumococcal vaccine2015

    • Author(s)
      H. Suzuki, A. Watari, E. Hashimoto, M. Yonemitsu, H. Kiyono, K. Yagi, M. Kondoh, and J. Kunisawa
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 5 Pages: e0126352-e0126352

    • DOI

      10.1371/journal.pone.0126352

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Use of cell-based screening to identify small-molecule compounds that modulate claudin-4 expression2015

    • Author(s)
      Watari A., Hashegawa M., Muangman T., Yagi K., Kondoh M.
    • Journal Title

      Biotechnology Letters

      Volume: 37(6) Issue: 6 Pages: 1177-85

    • DOI

      10.1007/s10529-015-1791-7

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Discovery of anti-claudin-1 antibodies as candidate therapeutics against hepatitis C virus2015

    • Author(s)
      Mayo Yamashita, Manami Iida, Minoru Tada, Yohitaka Shirasago, Masayoshi Fukasawa, Shotaro Nagase, Akihiro Watari, Akiko Ishii-Watabe, Kiyohito Yagi, Masuo Kondoh
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 353 Issue: 1 Pages: 112-118

    • DOI

      10.1124/jpet.114.217653

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Homoharringtonine increases intestinal epithelial permeability by modulating specific claudin isoforms in Caco-2 cell monolayers2015

    • Author(s)
      Akihiro Watari, Maki Hasegawa, Kiyohito Yagi, Masuo Kondoh
    • Journal Title

      Eur J Pharm Biopharm

      Volume: 89 Pages: 232-238

    • DOI

      10.1016/j.ejpb.2014.12.012

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of an anti-claudin-3 and -4 bispecific monoclonal antibody for cancer diagnosis and therapy2014

    • Author(s)
      Xiangru Li, Manami Iida, Minoru Tada, Akihiro Watari, Yumi Kawahigashi, Yuka Kimura, Taku Yamashita, Akiko Ishii-Watabe, Tadayuki Uno, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 351 Issue: 1 Pages: 206-213

    • DOI

      10.1124/jpet.114.216911

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Tight junction binderによる核酸医薬の経口投与法開発に関する基盤研究2016

    • Author(s)
      渡利彰浩、藤原果奈、渡辺知恵、仁科一隆、永田哲也、近藤昌夫、横田隆徳、村上正裕、八木清仁
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tricellular tight junctionを標的とした新規バリア制御技術、angubindin-1の開発2016

    • Author(s)
      山本浩樹、井口大輔、早石知浩、Susanne M. Krug、Michael Fromm、渡利彰浩、岡田欣晃、竹田浩之、永浜政博、土井健史、澤崎達也、近藤昌夫、八木清仁
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tight junction binderによる上皮バリア制御時における遺伝子発現変動の解析2016

    • Author(s)
      関昌孝、井口大輔、早石知浩、吉田有裕美、渡利彰浩、近藤昌夫、八木清仁
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Claudinを標的とした創薬基盤技術の開発~claudin-4を標的としたがん治療戦略の有効性及び安全性の評価~2016

    • Author(s)
      松田基、橋本洋佑、川東祐美、畑智幸、渡利彰浩、近藤昌夫、岡田欣晃、土井健史、八木清仁、多田稔、石井明子、深澤征義
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Safety profile and anti-tumor activity of a new generated human/mouse cross-reactive Anti-claudin-4 monoclonal antibody in mice2015

    • Author(s)
      Y. Hashimoto, Y. Kawahigashi, T. Hata, Y. Kimura, A. Watari, M. Kondoh, K. Yagi
    • Organizer
      European Cancer Congress 2015
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tricellular tight junction binder,angubindin-1の創製とバリア制御活性解析2015

    • Author(s)
      井口大輔、早石知浩、Susanne M. Krug、竹田浩之、Michael Fromm、渡利彰浩、澤崎達也、八木清仁、近藤昌夫
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Claudin-1を標的とした経皮吸収促進の可能性2015

    • Author(s)
      中嶋美咲、山下真代、渡利彰浩、深澤征義、八木清仁、近藤昌夫
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Anti-human claudin-1 monoclonal antbodies as anti-Hepatitis C Virus agents.2014

    • Author(s)
      M. Iida, M. Yamashita, S. Nagase, M. Tada, Y. Shirasago, M. Fukasawa, A. Watari, A. Ishii-Watabe, K. Yagi, M. Kondoh
    • Organizer
      Antibody Engineering & Therapeutics 2014
    • Place of Presentation
      Huntington Beach, CA, U.S.A.
    • Year and Date
      2014-12-07 – 2014-12-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Epitope mapping of an anti-claudin-1 monoclonal antibody and its application to preclinical drug discovery.2014

    • Author(s)
      T. Hata, S. Nagase, Y. Shirasago, M. Fukasawa, A. Watari, K. Yagi, M. Kondoh
    • Organizer
      Antibody Engineering & Therapeutics 2014
    • Place of Presentation
      Huntington Beach, CA, U.S.A.
    • Year and Date
      2014-12-07 – 2014-12-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of a Novel Bispecific Anti-Claudin Antibody and its Anti-Tumor Activity2014

    • Author(s)
      Y. Kimura, X. Li, M. Iida, M. Tada, A. Watabe-Ishii, M. Fukasawa, Y. Kawahigashi, A. Watari, K. Yagi, M. Kondoh
    • Organizer
      Antibody Engineering & Therapeutics 2014
    • Place of Presentation
      Huntington Beach, CA, U.S.A.
    • Year and Date
      2014-12-07 – 2014-12-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of an angulin binder and its tricellular tight junction-modulating activity2014

    • Author(s)
      D. Iguchi, S. M. Krug, T. Hayaishi, A. Watari, M. Nagahama, M. Flomm, K. Yagi, M. Kondoh
    • Organizer
      The 2014 ASCB / IFCB meeting
    • Place of Presentation
      Pennsylvania, U.S.A.
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA damageが誘導する腸管上皮バリアの機能亢進2014

    • Author(s)
      渡利 彰浩、長谷川 真希、八木 清仁、近藤 昌夫
    • Organizer
      37回日本分子生物学会年会
    • Place of Presentation
      神奈川県、横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of a novel strategy for the enhancement of drug absorption tarageting Claudin2014

    • Author(s)
      M. Iida, H. Suzuki, X. Li, A. Watari, M. Kondoh, and K. Yagi
    • Organizer
      第12回 プロテイン・アイランド 松山国際学術シンポジウム
    • Place of Presentation
      愛媛県、松山市
    • Year and Date
      2014-09-17
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi