| 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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