2012 Fiscal Year Final Research Report
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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| Keywords | インテグリン / Smad / 線維化 / 眼 / マウス |
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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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[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)
Pages: 501-11
DOI
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
Peer Reviewed
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