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Mechanism of the regulation of epithelial function by hydrostatic pressure and the application for canter treatment

Research Project

Project/Area Number 16K21101
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
General physiology
Research InstitutionKyoto University

Principal Investigator

Tokuda Shinsaku  京都大学, 医学研究科, 医員 (00433277)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsタイトジャンクション / 浸透圧 / アクチン / クローディン / 静水圧 / 癌 / 細胞極性 / 細胞増殖 / プロテインキナーゼA
Outline of Final Research Achievements

In this study, I attempted to elucidate the mechanism of the regulation of epithelial functions by the extracellular environment.
In MDCK cells, I revealed that claudin-2, transmembrane proteins in tight junctions, act as the sensor of the osmotic gradient between apical and basal sides to regulate several cell functions including transepithelial transport and cytoskeleton. Furthermore, I succeeded in establishing claudin-2 and claudin-4 double knockout cells and revealed the physiological role of claudin-4.
This study elucidates the mechanism in the epithelial cells to sense extracellular environment and regulate cell functions. This study also contributes to set a foundation for the clinical application for the cancer therapy in the future.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

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

  • [Journal Article] Claudin-4 knockout by TALEN-mediated gene targeting in MDCK cells: Claudin-4 is dispensable for the permeability properties of tight junctions in wild-type MDCK cells2017

    • Author(s)
      Tokuda Shinsaku、Hirai Toyohiro、Furuse Mikio
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 8 Pages: e0182521-e0182521

    • DOI

      10.1371/journal.pone.0182521

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of osmolality on paracellular transport in MDCK II cells2016

    • Author(s)
      Tokuda S, Hirai T, Furuse M
    • Journal Title

      PLoS One

      Volume: 11

    • NAID

      120005980913

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Effects of claudin-2 and claudin-4 knockouts in MDCK II cells2016

    • Author(s)
      Tokuda S, Hirai T, Furuse M
    • Organizer
      International conference "Tight junctions and their proteins"
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2016-08-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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