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Development of new drugs based on molecular mechanism for infectious corneal ulcer

Research Project

Project/Area Number 23592572
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionYamaguchi University

Principal Investigator

KIMURA Kazuhiro  山口大学, 医学部附属病院, 講師 (60335255)

Co-Investigator(Kenkyū-buntansha) SONODA Koh-hei  山口大学, 大学院医学系研究科, 教授 (10294943)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords角膜潰瘍 / 感染 / コラーゲン分解 / MMP / コラーゲン分解 / 角膜 / 潰瘍 / 角膜線維芽細胞 / 性ホルモン
Research Abstract

Collagen degradation of corneal stroma relates to the etiology of corneal ulcerration.Moreover,Corneal fibroblasts contribute to collagen remodeling in the corneal stroma in part by mediating collagen degradation.Corneal structure is influenced by sex hormone status,we examined the effects of sex hormones on collagen degradation by corneal fibroblasts.17beta-Estradiol and progesterone,female sex hormones,inhibited interleukin (IL)-1beta-induced collagen degradation,whereas testosterone and DHEA had no such effect.MMP expression and activation in corneal fibroblasts exposed to IL-1beta were also inhibited by them.They nhibited the IL-1beta-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK.17beta-Estradiol also inhibited the IL-1beta-induced phosphorylation of IkappaB-alpha.Female sex hormones inhibited MMP expression and activity in IL-1beta-stimulated corneal fibroblasts and thereby suppressed collagen degradation by these cells.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2013 2012 2011

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (14 results)

  • [Journal Article] Role of the JNK Signaling PathWay in Downregulation of Connexin43 by TNF-αin Human Corneal Fibroblasts2013

    • Author(s)
      Kimura K, Orita T, Morishige N, Nishida T, Sonoda KH
    • Journal Title

      Curr Eye Res

      Volume: 38(9) Pages: 926-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide2013

    • Author(s)
      Kimura K, Morita Y, Orita T, Haruta J, Takeji Y, Sonoda KH
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54(4) Pages: 2752-60

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine and chemokine secretion induced by poly(I : C) through NF-κB and phosphoinositide 3-kinase signaling pathways in human corneal fibroblasts2013

    • Author(s)
      Orita T, Kimura K, Nishida T, Sonoda KH
    • Journal Title

      Curr Eye Res

      Volume: 38(1) Pages: 53-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of the JNK Signaling PathWay in Downregulation of Connexin43 by TNF-α in Human Corneal Fibroblasts.2013

    • Author(s)
      Kimura K, Orita T, Morishige N, Nishida T, Sonoda KH
    • Journal Title

      Curr Eye Res

      Volume: 38(9) Pages: 926-932

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide.2013

    • Author(s)
      Kimura K, Morita Y, Orita T, Haruta J, Takeji Y, Sonoda KH
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54(4) Pages: 2752-2760

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts2012

    • Author(s)
      Zhou H, Kimura K, Orita T, Nishida T, Sonoda KH
    • Journal Title

      Investigative Ophthalmology & Vis ual Science

      Volume: 53(7) Pages: 4213-4219

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of common secreted factors in human corneal fibroblasts exposed to LPS, poly(I : C), or zymosan2012

    • Author(s)
      Kimura K, Orita T, Nomi N, Fujitsu Y, Nishida T, Sonoda KH
    • Journal Title

      Exp Eye Res

      Volume: 96(1) Pages: 157-162

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts.2012

    • Author(s)
      Zhou H, Kimura K, Orita T, Nishida T, Sonoda KH
    • Journal Title

      Investigative Ophthalmology & Vis ual Science

      Volume: 53 Pages: 4213-4219

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of common secreted factors in human corneal fibroblasts exposed to LPS, poly(I:C), or zymosan.2012

    • Author(s)
      Kimura K, Orita T, Nomi N, Fujitsu Y, Nishida T, Sonoda KH
    • Journal Title

      Exp Eye Res

      Volume: 96 Pages: 157-162

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 内科医のための眼科の知識2011

    • Author(s)
      木村和博,園田康平
    • Journal Title

      日本臨床内科医会会誌

      Volume: 26(2) Pages: 242-245

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells2011

    • Author(s)
      Kimura K, Teranishi S, Kawamoto K, Nishida T
    • Journal Title

      Exp Eye Res

      Volume: 92(5) Pages: 388-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role ofβ-Pix in corneal epithelial cell migration on fibronectin2011

    • Author(s)
      Kimura K, Teranishi S, Orita T, Zhou H, Nishida T
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 52(6) Pages: 3181-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 眼表面炎症疾患による角膜の細胞間接着機構への作用2011

    • Author(s)
      木村和博
    • Journal Title

      眼炎症学会誌

      Volume: 13(0) Pages: 7-11

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 炎症性サイトカインtumor necrosis factor-αによる培養角膜上皮バリアー破綻の機構2011

    • Author(s)
      木村和博
    • Journal Title

      日本眼科学会雑誌

      Volume: 4(11) Pages: 935-943

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of poly(I:C)-induced matrix metalloproteinase expression in human corneal fibroblasts by triptolide.2011

    • Author(s)
      Kimura K, Nomi N, Yan ZH, Orita T, Nishida T.
    • Journal Title

      Molecular vision

      Volume: 17 Pages: 526-532

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells.2011

    • Author(s)
      Kimura K, Teranishi S, Kawamoto K, Nishida T.
    • Journal Title

      Exp Eye Res.

      Volume: 92 Pages: 388-393

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 角膜混濁を伴う緑内障インプラント手術における23G内視鏡の使用例2013

    • Author(s)
      木村和博
    • Organizer
      第12回中四国眼科手術フォーラム
    • Place of Presentation
      広島県(シェラトン広島)
    • Year and Date
      2013-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 角膜実質細胞におけるGap junction阻害剤のコラーゲン分解への影響2013

    • Author(s)
      木村和博,折田朋子,能美典正,藤津揚一朗,西田輝夫,園田康平
    • Organizer
      第45回日本結合組織学会学術大会・第60回マトリックス研究会大会合同学術大会
    • Place of Presentation
      和歌山県(和歌山県立医科大学)
    • Year and Date
      2013-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 網膜色素上皮細胞におけるSex hormoneによるコラーゲンゲル収縮への作用2013

    • Author(s)
      木村和博,折田朋子,永井智彦,能美典正,藤津揚一朗,鈴木克佳,園田康平
    • Organizer
      日本眼科学会総会
    • Place of Presentation
      東京都(東京都国際フォーラム)
    • Year and Date
      2013-04-04
    • Related Report
      2013 Final Research Report
  • [Presentation] レチノイン酸による角膜潰瘍形成抑制の分子機序2013

    • Author(s)
      木村和博,園田康平
    • Organizer
      山口大学研究推進体「ストレス」成果報告シンポジウム
    • Place of Presentation
      山口県(山口大学)
    • Year and Date
      2013-02-08
    • Related Report
      2013 Final Research Report
  • [Presentation] 角膜実質細胞におけるGap junctionを介した細胞間ネットワークの炎症への作用2013

    • Author(s)
      木村 和博, 折田 朋子,能美 典正,藤津 揚一朗,西田 輝夫,園田 康平
    • Organizer
      第17回眼創傷治癒研究会
    • Place of Presentation
      広島県(グランドプリンスホテル広島)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 角膜実質細胞におけるGap junction阻害剤のコラーゲン分解への影響2013

    • Author(s)
      木村 和博, 折田 朋子,能美 典正,藤津 揚一朗,西田 輝夫,園田 康平
    • Organizer
      第45回日本結合組織学会学術大会・第60回マトリックス研究会大会 合同学術大会
    • Place of Presentation
      和歌山県(和歌山県立医科大学)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 網膜色素上皮細胞におけるSex hormoneによるコラーゲンゲル収縮への作用2013

    • Author(s)
      木村 和博, 折田 朋子,永井 智彦,能美 典正,藤津 揚一朗,鈴木 克佳,園田 康平
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京都(東京都国際フォーラム)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of the JNK Signaling Pathway in Down-Regulation of Connexin43 by TNF-αin Human Corneal Fibroblasts2012

    • Author(s)
      Orita T, Kimura K, Sonoda KH
    • Organizer
      2012 ARVO Annual Meeting
    • Place of Presentation
      FLORIDA,USA
    • Year and Date
      2012-05-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 角膜線維芽細胞におけるMedroxyprogesterone Acetateによるコラーゲン分解抑制作用2012

    • Author(s)
      木村和博,折田朋子,能美典正,藤津揚一朗,西田輝夫,園田康平
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京都(東京国際フォーラム)
    • Year and Date
      2012-04-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Sex-hormoneのコラーゲンゲル分解・収縮への作用2012

    • Author(s)
      木村和博
    • Organizer
      第16回眼科分子生物学研究会
    • Place of Presentation
      熊本県(八千代座交流施設)
    • Year and Date
      2012-02-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 角膜線維芽細胞におけるMedroxyprogesterone Acetateによるコラーゲン分解抑制作用2012

    • Author(s)
      木村 和博, 折田 朋子,能美 典正,藤津 揚一朗,西田 輝夫,園田 康平
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 角膜感染症における角膜実質細胞の機能2011

    • Author(s)
      木村和博
    • Organizer
      第48回日本眼感染症学会
    • Place of Presentation
      京都府(京都国際会館)
    • Year and Date
      2011-07-08
    • Related Report
      2013 Final Research Report
  • [Presentation] 角膜上皮細胞に対するホウ酸の影響2011

    • Author(s)
      寺西慎一郎,近間泰一郎,木村和博,園田康平
    • Organizer
      第115回日本眼科学会総会
    • Place of Presentation
      東京都(東京国際フォーラム)
    • Year and Date
      2011-05-13
    • Related Report
      2013 Final Research Report
  • [Presentation] β-PIXの活性化を介したフィブロネクチンによる細胞移動の制御2011

    • Author(s)
      木村和博,寺西慎一郎,折田朋子,西田輝夫,園田康平
    • Organizer
      第115回日本眼科学会総会
    • Place of Presentation
      東京都
    • Year and Date
      2011-05-13
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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