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

Molecular physiology of tight junction Claudin-family based on structural analysis

Research Project

Project/Area Number 16H05121
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOsaka University

Principal Investigator

Tamura Atsushi  大阪大学, 生命機能研究科, 特任准教授 (00362525)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsクローディン / タイトジャンクション / 上皮細胞 / 細胞間接着装置 / 上皮細胞間バリア / 構造解析 / 炎症 / 生体機能 / 分子動力学 / 微小環境 / ノックアウトマウス / 細胞間接着 / 細胞間バリア / 遺伝子改変マウス / ストランド / ノックアウト / 分子生理学
Outline of Final Research Achievements

Epithelial cells are the largest number of cells in the body that cover the internal and external surfaces of multicellular organisms. They are responsible for the functions and structures of major organs such as the skin, liver, and kidneys. The TJ (Tight Junction), composed of the polymer of claudin (Cldn) family protein molecules, reside in between epithelial cells. The paracellular permeability is mainly determined to maintain the tissue microenvironment properly. Biological functions are carried out within the exactly regulated tissue microenvironment. The failure of it is linked to various pathological conditions directly. In this application, we generate the Cldn null epithelial cells by using the CRISPR/CAS9 system to advance the functional analysis of Cldn-based TJ.

Academic Significance and Societal Importance of the Research Achievements

多細胞生物は、隣り合う上皮細胞同士が接着することで形成された上皮細胞シートにより、体内環境と体外環境が隔絶されることで、体内環境を維持する。このとき、適切に制御された上皮細胞シートバリアが必要である。上皮細胞シートバリアが重度に障害されると、脱水や生命に必要な酵素活性低下し生命も脅かされる。より軽度であっても、炎症や栄養分吸収障害などの機能障害を惹起する場合がある。申請者は、上皮細胞シートバリアの中でも、特に、上皮細胞間バリアに関わるタイトジャンクションおよびその構成タンパク質クローディンの構造と機能解析を進めている。胃酸と炎症など、今後の展開により疾患の治療と予防につながる成果が得られた。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (6 results)

  • [Int'l Joint Research] ハーバード大学/病理学教室(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Reciprocal association between the apical junctional complex and AMPK: A promising therapeutic target for epithelial/endothelial barrier function?2019

    • Author(s)
      Tsukita, K., Yano, T., Tamura, A., and Tsukita, S.
    • Journal Title

      Int J Mol Sci.

      Volume: 20 Issue: 23 Pages: 6012-6012

    • DOI

      10.3390/ijms20236012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions2019

    • Author(s)
      Konishi S, Yano T, Tanaka H, Mizuno T, Kanoh H, Tsukita K, Namba T, Tamura A, Yonemura S, Gotoh S, Matsumoto H, Hirai T, Tsukita S.
    • Journal Title

      Life Sci Alliance

      Volume: 2 Issue: 4 Pages: e201900414-e201900414

    • DOI

      10.26508/lsa.201900414

    • NAID

      120007144472

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of Stomach-Type Claudin-18 in Mice Induces Gastric Tumor Formation Independent of H pylori Infection2019

    • Author(s)
      Suzuki K, Sentani K, Tanaka H, Yano T, Suzuki K, Oshima M, Yasui W, Tamura A, Tsukita S.
    • Journal Title

      Cell Mol Gastroenterol Hepatol.

      Volume: 8 Issue: 1 Pages: 119

    • DOI

      10.1016/j.jcmgh.2019.03.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphologic determinant of tight junctions revealed by claudin-3 structures2019

    • Author(s)
      Nakamura Shun、Irie Katsumasa、Tanaka Hiroo、Nishikawa Kouki、Suzuki Hiroshi、Saitoh Yasunori、Tamura Atsushi、Tsukita Sachiko、Fujiyoshi Yoshinori
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 816-816

    • DOI

      10.1038/s41467-019-08760-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5 <sup>+</sup> Stem Cells via Inhibition of Wnt and Notch Signaling2019

    • Author(s)
      Zha JM, Li HS, Lin Q, Kuo WT, Jiang ZH, Tsai PY, Ding N, Wu J, Xu SF, Wang YT, Pan J, Zhou XM, Chen K, Tao M, Odenwald MA, Tamura A, Tsukita S, Turner JR, He WQ. Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5(+) Stem Cells via Inhibition of Wnt and Notch Signaling.
    • Journal Title

      Cell Mol Gastroenterol Hepatol.

      Volume: 7 Issue: 2 Pages: 255

    • DOI

      10.1016/j.jcmgh.2018.09.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Claudins: From Tight Junctions to Biological Systems2019

    • Author(s)
      Tsukita Sachiko、Tanaka Hiroo、Tamura Atsushi
    • Journal Title

      Trends in Biochemical Sciences

      Volume: 44 Issue: 2 Pages: 141-152

    • DOI

      10.1016/j.tibs.2018.09.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Claudin-3 regulates bile canalicular paracellular barrier and cholesterol gallstone core formation in mice2019

    • Author(s)
      Tanaka H, Imasato M, Yamazaki Y, Matsumoto K, Kunimoto K, Delpierre J, Meyer K, Zerial M, Kitamura N, Watanabe M, Tamura A, Tsukita S.
    • Journal Title

      J Hepatol.

      Volume: 69 Issue: 6 Pages: 1308

    • DOI

      10.1016/j.jhep.2018.08.025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Claudin-3 Loss Causes Leakage of Sweat from the Sweat Gland to Contribute to the Pathogenesis of Atopic Dermatitis2017

    • Author(s)
      Yamaga Kosuke、Murota Hiroyuki、Tamura Atsushi、Miyata Hirofumi、Ohmi Masato、Kikuta Junichi、Ishii Masaru、Tsukita Sachiko、Katayama Ichiro
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 138 Issue: 6 Pages: 1279

    • DOI

      10.1016/j.jid.2017.11.040

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Site-specific distribution of claudin-based paracellular channels with roles in biological fluid flow and metabolism2017

    • Author(s)
      Tanaka Hiroo、Tamura Atsushi、Suzuki Koya、Tsukita Sachiko
    • Journal Title

      Annals of the New York Academy of Sciences

      Volume: 1405 Issue: 1 Pages: 44

    • DOI

      10.1111/nyas.13438

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apical cytoskeletons and junctional complexes as a combined system in epithelial cell sheets2017

    • Author(s)
      Yano Tomoki、Kanoh Hatsuho、Tamura Atsushi、Tsukita Sachiko
    • Journal Title

      Annals of the New York Academy of Sciences

      Volume: 1405 Issue: 1 Pages: 32

    • DOI

      10.1111/nyas.13432

    • URL

      https://pure.teikyo.jp/en/publications/aab83b05-3cf1-4971-8738-2852c55fffd6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time- and dose-dependent claudin contribution to biological functions: Lessons from claudin-1 in skin2017

    • Author(s)
      Tokumasu Reitaro、Tamura Atsushi、Tsukita Sachiko
    • Journal Title

      Tissue Barriers

      Volume: 5 Issue: 3 Pages: e1336194-e1336194

    • DOI

      10.1080/21688370.2017.1336194

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-22Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance2017

    • Author(s)
      Tsai Pei-Yun、Zhang Bingkun、He Wei-Qi、Zha Juan-Min、Odenwald Matthew A.、Singh Gurminder、Tamura Atsushi、Shen Le、Sailer Anne、Yeruva Sunil、Kuo Wei-Ting、Fu Yang-Xin、Tsukita Sachiko、Turner Jerrold R.
    • Journal Title

      Cell Host & Microbe

      Volume: 21 Issue: 6 Pages: 671

    • DOI

      10.1016/j.chom.2017.05.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis2016

    • Author(s)
      Tokumasu R, Yamaga K, Yamazaki Y, Murota H, Suzuki K, Tamura A, Bando K, Furuta Y, Katayama I, Tsukita S.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 28

    • DOI

      10.1073/pnas.1525474113

    • URL

      https://localhost/en/publications/5bd814f2-392e-4903-a552-bdea5f86ccbc

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] タイトジャンクション - クローディンによる細胞間バリア制御と、その異 常と病態ークローディン欠損マウス解析の視点からー2019

    • Author(s)
      田村 淳、田中 啓雄、 矢野 智樹、鈴木 浩也、 月田 早智子
    • Organizer
      第71回日本細胞生物学会大会/ 第19回日本蛋白質科学会年会 合同大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of planar cell polarity-dependent distribution of apical microtubules in the coordinated ciliary beating of tracheal multiciliated cells.2018

    • Author(s)
      Shogo Nakayama, Elisa Herawati, Maki Takagishi, Takayuki Torisawa, Toshinori Namba, Tomoki Yano, Atsushi Tamura, Shuji Ishihara, Kazuhiro Oiwa, Masahide Takahashi, Sachiko Tsukita
    • Organizer
      ASCB 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] TJ-MAP4 up-regulates the level of ppMLC at the circumferential ring for epithelial apical constriction2018

    • Author(s)
      Hatsuho Kanoh, Tomoki Yano, Atsushi Tamura, Yuhei Goto, Shogo Nakayama, Akira Komatsubara, Kazuhiro Aoki and Sachiko Tsukita
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Continuous Gastric Acid Leakage due to Dysfunctional Paracellular-Barrier Function Causes Gastric Tumor via CXCL5 and Wnt Signaling with Aging2018

    • Author(s)
      Koya Suzuki, Kazuhiro Sentani, Hiroo Tanaka, Tomoki Yano, Kazuo Suzuki, Atsushi Tamura, Sachiko Tsukita,
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Establishment of a PCP-dependent apical microtubule network in tracheal MCCs2018

    • Author(s)
      Shogo Nakayama, Elisa Herawati, Maki Takagishi, Tomoki Nishida, Kanako Inoue, Takayuki Torisawa, Toshinori Namba, Shuji Ishihara, Hiroo Tanaka, Tomoki Yano, Atsushi Tamura, Kazuhiro Oiwa, Masahide Takahashi, SachikoTsukita
    • Organizer
      Joint Annual Meeting Of JSDB 51st and JSCB 70th(第70回日本細胞生物学会・第53回日本発生生物学会合同大会)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Tight junctional cingulin organizes the apical intermediate filaments2018

    • Author(s)
      Yuki Nakao, Hiroo Tanaka, Tomohiro Tamura, Shogo Nakayama, Akira Yamamoto, Hatsuho Kanoh, Atsushi Tamura, Tomoki Yano, Sachiko Tsukita
    • Organizer
      Joint Annual Meeting Of JSDB 51st and JSCB 70th(第70回日本細胞生物学会・第53回日本発生生物学会合同大会)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 上皮細胞シート形態形成におけるタイトジャンクション微小管結合タンパク質の解析2017

    • Author(s)
      加納初穂、矢野智樹、氏昌未、田村朋宏、田村淳、月田早智子
    • Organizer
      第69回 日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] クローディン15における細胞間チャネル機能のイオン選択性とサイズ選択性制御機構の検討2017

    • Author(s)
      鈴木浩也、武知真希、谷一寿、田村淳、藤吉好則、月田早智子
    • Organizer
      第69回 日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 気管多繊毛上皮細胞における繊毛配列動態2017

    • Author(s)
      月田早智子、加納初穂、Elisa Herawati、小西聡史、立石和博、 矢野智樹、田村淳
    • Organizer
      第69回 日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] タイトジャンクション構成タンパク質クローディンが規定する生体微小環境恒常性と消化管機能2017

    • Author(s)
      田村淳、田中啓雄、高橋信之、月田早智子
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      京都女子大
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Bile flow and gallstone diseases induced by the deficiency of claudin family proteins2016

    • Author(s)
      Atsushi Tamura
    • Organizer
      International conference Tight junction and their proteins
    • Place of Presentation
      Germany
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 大阪大学大学院生命機能研究科

    • URL

      http://www.fbs.osaka-u.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 大阪大学大学院生命機能研究科 月田研究室

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/tsukita/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 大阪大学月田研究室

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/tsukita/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪大学生命機能研究科

    • URL

      http://www.fbs.osaka-u.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪大学医学系研究科

    • URL

      http://www.med.osaka-u.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪大学大学院生命機能研究科/医学系研究科 月田研究室

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/tsukita/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi