| Project/Area Number |
15591871
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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 Wakayama Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (40254544)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Transforming growth factor beta / Proliferative vitreoretinopathy / retinal pigment epithelium / Epithelial-mesenchymal transition / Smad / Signal transduction / Gene therapy / Adenoviral vector / トランスフォーミング成長因子ベータ / 増殖硝子体網膜症 / 上皮-間葉系移行 / ノックアウトマウス / 細胞培養 |
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| Research Abstract |
Objective: Retinal pigment epithelium is known to undergo epithelial-mesenchymal transition (EMT), which is mediated mainly by transforming growth factor b (TGFb)/Smad2(3)4 signaling. Smad7 suppresses such signaling by blocking this Smad complex from entering the nucleus. Accordingly, we determined the effects of Smad7 gene transfer in prevention of fibrogenic responses by retinal pigment epithelium, one of the major causes of post-retinal detachment proliferative vitreoretinopathy (PVR) in mice.
Methods: Retinal detachment induced PVR in a mouse model. An eye received either an adenoviral gene transfer of Smad7 or Cre recombinase gene only. The eyes were histologically analyzed. A retinal pigment epithelial cell line, ARPE-19, was used to determine if Smad7 gene transfection suppresses the fibrogenic response to TGFb2exposure.
Results: Smad7 gene transfer inhibited TGFb2/Smad signaling in ARPE 19 cells and expression of collagen type I and TGFb1, but had no effect on their basal levels. In vivo Smad7 overexpression resulted in suppression of Smad2/3 signals and of the fibrogenic response to EMT by retinal pigment epithelium.
Conclusion: Smad7 gene transfer suppresses fibrogenic responses to TGFb2 by retinal pigment epithelial cells in vitro and in vivo.
Clinical relevance: Smad7 gene transfer might be a new strategy to prevent and treat PVR.
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