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The function of Cldn6 signaling during the differentiation from stem cells to epithelial cells

Research Project

Project/Area Number 24790390
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionFukushima Medical University

Principal Investigator

TOMIKAWA Naoki  福島県立医科大学, 医学部, 講師 (80468587)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生医学 / 幹細胞 / 上皮細胞 / 上皮分化 / タイト結合 / 国際情報交換
Research Abstract

We hypothesis that claudin-6 (Cldn6), tight junction protein, function as the coordinator in the differentiation from stem cells to epithelial cells. In mouse F9 stem cell lines and embryonic stem cells, the expression of Cldn6 increased other tight junction protein and induced the differentiation to mature epithelial cells. Moreover, the localization of Cldn6 to cell-cell adhesion, second extracellular domain of Cldn6, and 196 and 200 tyrosine residues in C-terminal intracellular domain of Cldn6 were essential for Cldn6-induced epithelial differentiation. In addition, Cldn6 interacted with src-family kinases (SFKs), and then activated SFKs phosphorylated 196 and 200 tyrosine residues in Cldn6. These results indicate that Cldn6 and SFKs cooperatively induced the signaling for epithelial differentiation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (24 results)

All 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (8 results) Book (3 results) Remarks (4 results)

  • [Journal Article] The Tight-Junciton Protein Claudin-6 Induces Epithelila Differentiation from Mouse F9 and Embryonic Stem Cells2013

    • Author(s)
      Sugimoto K, Ichikawa-Tomikawa N, Satohisa S, Akashi Y, Kanai R, Saito T, Sawada N, Chiba H
    • Journal Title

      PLoS One

      Volume: 8 (10)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Ichikawa-Tomikawa N, Arikawa-Hirasawa E. Laminin-1 promotes enteric nervous system development in mouse embryo2013

    • Author(s)
      Nakazawa N, Miyahara K, Okawada M, Yamataka A, Suzuki R, Akazawa C
    • Journal Title

      Pediatric Surgery International

      Volume: 29 (11) Pages: 1205-8

    • Related Report
      2013 Final Research Report
  • [Journal Article] Synovial prelecan is required for osteophyte formation in knee osteoarthritis2013

    • Author(s)
      Kaneko H, Ishijima M, Furami I, Ichikawa-Tomikawa N, Kosaki K, Sadatsuki R, Yamada Y, Kurosawa H, Kaneko K, and Arikawa-Hirasawa E
    • Journal Title

      Matrix Biology

      Volume: 32 Pages: 178-87

    • Related Report
      2013 Final Research Report
  • [Journal Article] The Tight-Junciton Protein Claudin-6 Induces Epithelila Differentiation from Mouse F9 and Embryonic Stem Cells.2013

    • Author(s)
      Sugimoto K*, Ichikawa-Tomikawa N*, Satohisa S, Akashi Y, Kanai R, Saito T, Sawada N, Chiba H.
    • Journal Title

      PloS One

      Volume: 8 Issue: 10 Pages: e75106-e75106

    • DOI

      10.1371/journal.pone.0075106

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synovial perlecan is required for osteophyte formation in knee osteoarthritis2013

    • Author(s)
      Kaneko H, Ishijima M, Futami I, Ichikawa N, Yamada Y, Kurosawa H, Kaneko K, Arikawa-Hirasawa E
    • Journal Title

      Matrix Biol

      Volume: 32 Issue: 3-4 Pages: 178-187

    • DOI

      10.1016/j.matbio.2013.01.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolation and characterization of multi-potential mesenchymal cells from the mouse synovium2012

    • Author(s)
      Futami I, Ishijima M, Kaneko H, Tsuji K, Ichikawa-Tomikawa N, Sadatsuki R, Muneta T, Arikawa-Hirasawa E, Sekiya I, and Kaneko K
    • Journal Title

      PLoS One

      Volume: 7(9)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Isolation and characterization of multipotential mesenchymal cells from the mouse synovium.2012

    • Author(s)
      Futami I
    • Journal Title

      PLoS One.

      Volume: 7(9) Issue: 9 Pages: e45517-e45517

    • DOI

      10.1371/journal.pone.0045517

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laminin 〓lphal is essential for mouse cerebellar development2012

    • Author(s)
      Ichikawa-Tomikawa N
    • Journal Title

      Matrix Biology

      Volume: 31 Issue: 1 Pages: 17-28

    • DOI

      10.1016/j.matbio.2011.09.002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lamininα1 regulates age-related mesangial cell proliferation and mesangial matrix accumulation through the TGFβpathway

    • Author(s)
      Ning L, Kurihara H, Vega S, Ichikawa-Tomikawa N, Xu Z, Nonaka R, Kazuno S, Yamada Y, Miner JH, Arikawa-Hirasawa E
    • Journal Title

      Am J Pathol

      Volume: (In press)

    • Related Report
      2013 Final Research Report
  • [Presentation] Claudin-6-mediated cell adhesion induces intracellular signaling for epithelial morphogenesis in mouse F9 and embryonic stem cells2013

    • Author(s)
      Naoki Tomikawa, Kotaro Sugimoto, Hideki Chiba
    • Organizer
      第65回日本細胞生物学会大会 シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] クローディン-6による幹細胞の新規上皮分化誘導機構2013

    • Author(s)
      冨川直樹、杉本幸太郎、金居李紗、田中瑞子、杉野隆、千葉英樹
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌、ワークショップ
    • Related Report
      2013 Final Research Report
  • [Presentation] Claudin-6-mediated cell adhesion induces intracellular signaling for epithelial morphogenesis in mouse F9 and embryonic stem cells2013

    • Author(s)
      Naoki Tomikawa
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] クローディン-6による幹細胞の新規上皮分化誘導機構2013

    • Author(s)
      冨川 直樹
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Src family kinase involves in the differentiation of stem cells to epithelila cells2012

    • Author(s)
      Naoki Tomikawa-Ichikawa, Kotaro Sugimoto, Risa Kanai, Hideki Chiba
    • Organizer
      International Tight Junction Conference
    • Place of Presentation
      Merida. Mexico. Oral presentation
    • Related Report
      2013 Final Research Report
  • [Presentation] クローディン-6によるF9幹細胞の上皮分化へのsrc family kinaseの関与2012

    • Author(s)
      冨川-市川直樹、杉本幸太郎、金居李紗、田中瑞子、杉野隆、千葉英樹
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京、ポスター発表
    • Related Report
      2013 Final Research Report
  • [Presentation] Src family kinase involves in the differentiation of stem cells to epithelial cells2012

    • Author(s)
      Naoki Tomikawa-Ichikawa, Kotaro Sugimoto, Risa Kanai1, Hideki Chiba
    • Organizer
      International Tight Junction Conference
    • Place of Presentation
      Merida, Mexico
    • Related Report
      2012 Research-status Report
  • [Presentation] クローディン-6によるF9幹細胞の上皮分化へのsrc family kinase の関与2012

    • Author(s)
      冨川 直樹、杉本 幸太郎、金居 李紗、田中 瑞子、杉野 隆、千葉 英樹
    • Organizer
      第101回 日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Book] 蛍光ダイレクトラベリングによる生細胞蛍光イメージングSurgery Frontier. 19 (3).2012

    • Author(s)
      冨川直樹、千葉英樹
    • Related Report
      2013 Final Research Report
  • [Book] Stereotaxic injectionの手法と応用Surgery Frontier. 19 (4).2012

    • Author(s)
      冨川直樹、千葉英樹
    • Related Report
      2013 Final Research Report
  • [Book] SURGERY FRONTIER2012

    • Author(s)
      冨川直樹、千葉英樹
    • Total Pages
      5
    • Publisher
      メディカルレビュー
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.fmu.ac.jp/home/p2/sub3.html

    • Related Report
      2013 Final Research Report
  • [Remarks] Facebook

    • Related Report
      2013 Final Research Report
  • [Remarks] 福島県立医科大学基礎病理学講座

    • URL

      http://www.fmu.ac.jp/home/p2/sub3.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 公立大学法人 福島県立医科大学 基礎病理学講座

    • URL

      http://www.fmu.ac.jp/home/p2/sub4.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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