Development of a new strategy for the prevention of ocular tissue fibrosis by targeting integrin-Smad craootalks
| Project/Area Number |
22591948
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
SAIKA Shizuya 和歌山県立医科大学, 医学部, 教授 (40254544)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Yuka 和歌山県立医科大学, 医学部, 講師 (50264891)
SHIRAI Kumi 和歌山県立医科大学, 医学部, 講師 (70326370)
MIYAMOTO Takeshi 和歌山県立医科大学, 医学部, 講師 (20336879)
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| Project Period (FY) |
2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | インテグリン / Smad / 線維化 / 眼 / マウス / オステオポンチン / 中和抗体 / 創傷治癒 / 組織線維化 / アルカリ角膜外傷 / 水晶体外傷 / ミドルリンカー / テネイシン |
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| Research Abstract |
The expression of extracellular matrix components and fibrotic cytokines in fibroblasts, which were from either osteopontin (OPN) or tenascin C (TNC), both of which are ligands of a9 integrin, knock-out and wild-type mice, were examined. Lacking OPN or TNC decreased the expression of type I collagen, TGF-b1, and alpha-smooth muscle actin. However OPN signaling is directly involved in phosphorylation of Smad3 and p38, the lack of TNC did not affect Smad3 expression levels or phosphorylation. The effects of TNC knock-out on wound healing models, which were scar healing after corneal incision and corneal angiogenesis, were examined. The lack of TNC inhibited both scarring and angiogenesis. The effects of OPN knock-out on another wound healing models associated with angiogenesis, which were angiogenesis and scar tissue formation after laser irradiation on choroid and retina, were examined. The effects of dose of OPN neutralizing antibody were also examined before intraperitoneal administration of a9 integrin neutralizing antibody .Lacking OPN or blocking its signaling induced by systemic administration of an OPN neutralizing antibody suppressed the expression of inflammatory cytokines, choroidal neovascularization and scar tissue formation. Controlling OPN or TNC signaling would be a new treatment strategy for ocular scarring or diseases associated with angiogenesis.
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Report
(4 results)
Research Products
(74 results)
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[Journal Article] Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1-induced inflammatory responses to corneal injury.2012
Author(s)
Yang Y, Yang H, Wang Z, Varadaraj K, Kumari SS, Mergler S, Okada Y, Saika S, Kingsley PJ, Marnett LJ, Reinach PS.
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Journal Title
Cell Signal
Volume: 25(2)
Issue: 2
Pages: 501-11
DOI
Related Report
Peer Reviewed
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[Journal Article] Crosstalk between TGF-beta and MAPK signaling during corneal wound healing.2011
Author(s)
Terai K, Call MK, Liu H, Saika S, Liu CY, Hayashi Y, Chikama T, Zhang J, Terai N, Kao CW, Kao WW.
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 52(11)
Pages: 8208-15
Related Report
Peer Reviewed
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[Journal Article] Crosstalk between TGF-beta and MAPK signaling during corneal wound healing2011
Author(s)
Terai K, Call MK, Liu H, Saika S, Liu CY, Hayashi Y, Chikama T, Zhang J, Terai N, Kao CW, Kao WW
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 52(11)
Issue: 11
Pages: 8208-15
DOI
Related Report
Peer Reviewed
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[Journal Article] Epiplakin欠損での角膜創傷治癒2011
Author(s)
小門正英, 岡田由香, 石川一志, 後藤瑞生, 藤原作平, 雑賀司珠也
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Journal Title
日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集43回・58回Page136(2011.05)
Pages: 136-136
Related Report
Peer Reviewed
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[Presentation] 糖尿病と眼2011
Author(s)
雑賀司珠也
Organizer
最新の医療カンファランス
Place of Presentation
和歌山
Year and Date
2011-03-10
Related Report
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