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New treatment strategy for ocular fibrotic diseases by modulation of TGFbeta signal with TRP cation channnels

Research Project

Project/Area Number 25462729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionWakayama Medical University

Principal Investigator

Saika Shizuya  和歌山県立医科大学, 医学部, 教授 (40254544)

Co-Investigator(Kenkyū-buntansha) 住岡 孝吉  和歌山県立医科大学, 医学部, 講師 (40433362)
山中 修  和歌山県立医科大学, 医学部, 博士研究員 (50254545)
岡田 由香  和歌山県立医科大学, 医学部, 准教授 (50264891)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords組織瘢痕化 / 成長因子 / TRPイオンチャネル / 角膜 / 眼 / ノックアウトマウス / 細胞培養 / 水晶体 / TRPV4 / TRPA1 / イオンチャンネル / 創傷治癒 / 線維化 / シグナル / TRPチャネル / TGFβシグナル / Smad / MAPキナーゼ / 線維芽細胞 / 炎症 / 瘢痕
Outline of Final Research Achievements

Tissue fibrosis induced by an alkali exposure was effectively suppressed by TRP channel (TRPA1, TRPV1, TRPV4)-signals modulation of TGFbeta-MAPK/Smad signals in genetically modified mouse lines. The inhibitory effects was reproduced by specific chemical inhibitors of each channel. TRPV4 signal was also found to be related to interleukin-6 signal in tissue fibrosis. A similar mechanism might be invilved in conjunctival fibrosis, although we have preliminary data. Tissue fibrosis in a mouse lens related to epithelial-mesenchymal transition did not seem to be related to TRP cation channel signals.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (36 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 13 results,  Open Access: 10 results,  Acknowledgement Compliant: 3 results) Presentation (21 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (2 results)

  • [Journal Article] Bacteriology of the conjunctiva in pre-cataract surgery patients with occluded nasolacrimal ducts and the operation outcomes in Japanese patients.2017

    • Author(s)
      Hayashi Y, Miyamoto T, Fujita S, Tomoyose K, Ishikawa N, Kokado M, Sumioka T, Okada Y, Saika S.
    • Journal Title

      BMC Ophthalmol.

      Volume: 17 Issue: 1 Pages: 15-15

    • DOI

      10.1186/s12886-017-0410-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.2016

    • Author(s)
      Okada Y, Shirai K, Miyajima M, Reinach PS, Yamanaka O, Sumioka T, Kokado M, Tomoyose K, Saika S.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 12 Pages: e0167200-e0167200

    • DOI

      10.1371/journal.pone.0167200

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of epiplakin-knockdown in cultured corneal epithelial cells.2016

    • Author(s)
      Kokado M, Okada Y, Miyamoto T, Yamanaka O, Saika S.
    • Journal Title

      BMC Res Notes.

      Volume: 9 Issue: 1 Pages: 278-278

    • DOI

      10.1186/s13104-016-2082-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia.2016

    • Author(s)
      Morii T, Sumioka T, Izutani-Kitano A, Takada Y, Okada Y, Kao WW, Saika S.
    • Journal Title

      Case Rep Ophthalmol Med.

      Volume: 5687285 Pages: 5687285-5687285

    • DOI

      10.1155/2016/5687285

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice.2016

    • Author(s)
      Iwanishi H, Fujita N, Tomoyose K, Okada Y, Yamanaka O, Flanders KC, Saika S.
    • Journal Title

      Lab Invest.

      Volume: e-journal Issue: 6 Pages: 641-51

    • DOI

      10.1038/labinvest.2016.30

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transient Receptor Potential Channels and Corneal Stromal Inflammation.2015

    • Author(s)
      0kada Y,Reinach PS,Shirai K,Kitano-Izutani A,Miyajima M,Yamanaka O,Sumioka T, Saika S
    • Journal Title

      Cornea

      Volume: Suppl 11 Issue: Supplement 11 Pages: 136-41

    • DOI

      10.1097/ico.0000000000000602

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ocular transient receptor potential channel function in health and disease.2015

    • Author(s)
      Reinach PS, Mergler S, Okada Y, Saika S.
    • Journal Title

      BMC Ophthalmol.

      Volume: Suppl 1 Issue: S1 Pages: 153-153

    • DOI

      10.1186/s12886-015-0135-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea.2015

    • Author(s)
      Tomoyose K, Okada Y, Sumioka T, Miyajima M, Flanders KC, Shirai K, Morii T, Reinach PS, Yamanaka O, Saika S.
    • Journal Title

      J Ophthalmol.

      Volume: Sep 27 Pages: 706404-706404

    • DOI

      10.1155/2015/706404

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Temperature-sensitive transient receptor potential channels in corneal tissue layers and cells.2014

    • Author(s)
      Mergler S1, Valtink M, Takayoshi S, Okada Y, Miyajima M, Saika S, Reinach PS.
    • Journal Title

      Ophthalmic Res.

      Volume: 52 Issue: 3 Pages: 151-159

    • DOI

      10.1159/000365334

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPA1 is required for TGF-β signaling and its loss blocks inflammatory fibrosis in mouse corneal stroma.2014

    • Author(s)
      2.Okada Y, Shirai K, Reinach PS, Kitano-Izutani A, Miyajima M, Flanders KC, Jester JV, Tominaga M,Saika S
    • Journal Title

      Lab Invest.

      Volume: 94(9) Pages: 1030-41

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse.2014

    • Author(s)
      4.Sumioka T, Okada Y, Reinach PS, Shirai K, Miyajima M, Yamanaka O, Saika S:
    • Journal Title

      Vis Sci.

      Volume: 55(5) Pages: 3295-302

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Errors in the prediction of postoperative refraction following intraocular lens implantation in eyes with pseudoexfoliation syndrome2013

    • Author(s)
      Ishikawa N, Hayashi Y, Miyamoto T, Saika S
    • Journal Title

      J Cataract Refract Surg

      Volume: 39(4) Issue: 4 Pages: 649-650

    • DOI

      10.1016/j.jcrs.2013.02.023

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased fragility, impaired differentiation, and acceleration of migration of corneal epithelium of epiplakin-null mice.2013

    • Author(s)
      Kokado M, Okada Y, Goto M, Ishikawa K, Miyamoto T, Yamanaka O, Fujiwara S, Saika S
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54 Issue: 5 Pages: 3780-9

    • DOI

      10.1167/iovs.12-11077

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 網膜静脈分枝閉塞症に伴う黄斑浮腫に対する抗VEGF治療前後のM-CHARTSを用いた変視評価2016

    • Author(s)
      住岡孝吉、岩西宏樹、二出川裕香、森井智也、雑賀司珠也
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウス角膜創傷治癒過程におけるマトリセルラータンパク質の役割2016

    • Author(s)
      住岡孝吉、山中 修、岡田由香、雑賀司珠也
    • Organizer
      第48回日本結合組織学会
    • Place of Presentation
      長崎
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effects of loss of TRPV4 function on corneal epithelial wound healing in mice.2016

    • Author(s)
      Okada Y, Reinach PS, Miyajima M, Saika S.
    • Organizer
      he Association for Research in Vision and Ophthalmology Annual Meeting
    • Place of Presentation
      Seatle
    • Year and Date
      2016-05-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Relation of Tenascin X and VEGF in the corneal cauterization model2016

    • Author(s)
      Sumioka T, Okada Y, Yamanaka O, Nidegawa Y, Miyajima M, Matsumoto K, Saika S
    • Organizer
      The Association for Research in Vision and Ophthalmology Annual Meeting
    • Place of Presentation
      Seatle
    • Year and Date
      2016-05-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス神経麻痺性角膜症モデルに対する三叉神経節でのTRPV4強制発現による治療効果2016

    • Author(s)
      岡田由香、佐野裕美、小林憲太、富永真琴、南部敦、雑賀司珠也
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 角膜電熱凝固モデルにおけるテネイシンXとVEGFの関連2016

    • Author(s)
      住岡孝吉、岡田由香、山中 修、二出川裕香、宮嶋正康、松本健一、雑賀司珠也
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effects of loss of TRPV4 function on corneal epithelial wound healing in mice2016

    • Author(s)
      Yuka Okada1 , Peter S. Reinach2 , Masayasu Miyajima3 , Shizuya Saika1
    • Organizer
      Gordon Research Conferences
    • Place of Presentation
      カリフォルニア, アメリカ
    • Year and Date
      2016-02-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] TRPV4イオンチャネルの角膜上皮欠損の創傷治癒での役割2016

    • Author(s)
      岡田由香1、ピーター・ライナック2、住岡孝吉1、白井久美1、山中修1、宮嶋正康3、雑賀司珠也1
    • Organizer
      角膜カンファランス
    • Place of Presentation
      軽井沢
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
  • [Presentation] TRPA1イオンチャネルの角膜上皮欠損の創傷治癒での役割2015

    • Author(s)
      岡田由香1、ピーター・ライナック2、白井久美1、住岡孝吉1、山中修1、宮嶋正康3、雑賀司珠也1
    • Organizer
      第19t回眼創傷治癒研究会
    • Place of Presentation
      姫路
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Impairment of cornea epithelium wound healing in a TRPA1-deficient mouse2015

    • Author(s)
      Yuka Okada, Kumi Shirai, Peter Reinach, Masayasu Miyajima, Shizuya Saika
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) 2015 Annual Meeting
    • Place of Presentation
      コロラド,アメリカ
    • Year and Date
      2015-05-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞膜TRPA1イオンチャネルの角膜上皮欠損の創傷治癒での役割2015

    • Author(s)
      岡田由香1、ピーター・ライナック2、白井久美1、宮嶋正康3、雑賀司珠
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-04-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Roles of matricellular proteins in EMT of lens epithelium.2014

    • Author(s)
      Saika S:
    • Organizer
      The Catholic University of Korea講演会
    • Place of Presentation
      Korea
    • Year and Date
      2014-08-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Roles of TRP channels in Smad signal and myofibroblast formation in stromal repair2014

    • Author(s)
      Saika S:
    • Organizer
      Biennial Meeting of the International Society for Eye Research,
    • Place of Presentation
      San Francisco, CA
    • Year and Date
      2014-07-21 – 2014-07-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Lacking Smad3 attenuates development of Argon laser-induced CNV in mice2014

    • Author(s)
      Iwanishi H, Sumioka T, Okada Y, Yamanaka O, Saika S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2014-05-04 – 2014-05-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Immunohistochemical observation of meibomian gland following ocular surface alkali burning in wild-type and Smad3-deficient mice2014

    • Author(s)
      Mizoguchi S, Okada Y, Arita R, Saika S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2014-05-04 – 2014-05-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of β-catenin inhibitor, ICG-001, on cultured human conjunctival fibroblast2014

    • Author(s)
      Yamanaka O, Kao WW, Saika S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2014-05-04 – 2014-05-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Impaired angiogenic response in cornea by lacking tenascin X in mice2014

    • Author(s)
      Sumioka T, Okada Y, Nidegawa Y, Miyajima M, Matumoto K, Saika S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2014-05-04 – 2014-05-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of TRPV1 Ion Chnnel in Corneal Wound Healing

    • Author(s)
      Shizuya Saika
    • Organizer
      GAVIN HERBERT EYE INSTITYTE講演会
    • Place of Presentation
      USA
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Modulation of keratocyte-myofibroblast conversion by extracellular matrix in corneal stroma

    • Author(s)
      Shizuya Saika
    • Organizer
      GAVIN HERBERT EYE INSTITYTE講演会
    • Place of Presentation
      USA
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Prevention of Keratocyte-Myofibroblast conversion by Targeting Matrix-Cytokine System

    • Author(s)
      Shizuya Saika
    • Organizer
      Annual meeting of the Association for research in Vision and Ophthalmology
    • Place of Presentation
      USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Loss of Muc16 induces inflammatory reaction in conjunctiva and secondarily affects corneal epithelium and stroma in mice.

    • Author(s)
      Shizuya Saika
    • Organizer
      Gordon Research Conferences
    • Place of Presentation
      USA
    • Related Report
      2013 Research-status Report
  • [Book] Lens epithelium and posterior capsular opacification2014

    • Author(s)
      Shirai K, Kitano-Izutani A, Miyamoto T, Tanaka S, Saika S
    • Total Pages
      15
    • Publisher
      Springer Verlag
    • Related Report
      2014 Research-status Report
  • [Book] Lens epithelium and posterior capsular opacification2014

    • Author(s)
      2.Miyamoto T, Ishikawa N, Shirai K, Kitano-Izutani A, Tanaka S, Saika S
    • Total Pages
      11
    • Publisher
      Springer Verlag
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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