Investigation of the roles of Smad linker region phosphoryulation in epithelial-mesenchymal transition and tissue fibrosis.
| Project/Area Number |
19592036
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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, 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)
YAMANAKA Osamu 和歌山県立医科大学, 医学部, 講師 (50254545)
IKEDA Kazuo 大阪市立大学, 医学部・大学院, 准教授 (80275247)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 水晶体上皮細胞 / 網膜色素上皮細胞 / 線維芽細胞 / トランスフォーミング成長因子 / Smad / リン酸化 / 上皮-間葉系移行 / 線維化 / 増殖硝子体網膜症 / マウス / 水晶体外傷 / aTN4マウス水晶体細胞 / 免疫組織化学 / 水晶体上被細胞 / 網膜色素被細胞 / 繊維芽細胞 / 繊維化 / ミドルリンカー領域 / ウエスタンブロット / シグナル伝達 |
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| Research Abstract |
In cultures of retinal pigment epithelial cell line, ARPE-19 and mouse lens epithelial cell line, a-TN4, TGFbeta1 addition activates phosphorylation of Smad2/3 C-terminal and middle rinker region along with epithelial-mesenchymal transition (EMT). Phorphorylation of Smad2/3 middle lilnker was observed even under TGFbeta1-minus condition and seemed to be attenuated with inhibitors of MAPKs. Immunohistochemistry of human samples showed that EMT-lens cells exhibited phosphorylation of Smad3 middle renker region more prominently as compared with its C-terminus phosphrylation. C-terminus phosphorylation was not observed in smooth muscle action-positive cells. Rat lens injury experiments suggested that invlovement of JNK and p38 in Smad middle linker region phosphorylation. EMT-related gene expression was overall detecterd in mosue proliferative vitreoretinopathy (PVR) model. Immunohistochemistry showed both C-terminus and middle linker region phosphorylations of Smad3. Adenoviral overexpression of dominant negative p38 seemed to suppress middle linker region phosphorylation of Smad3. Investigations on human samples and its animal model, as well as cell culture experiments, suggetsed involvement of Smad3 middle linker region phosphorylation in EMT-related fibrogenic ocular pathologies.
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] Impaired angiogenic response in the corneas of mice lacking osteopontin.2009
Author(s)
Fujita N, Fujita S, Okada Y, Fujita K, Kitano A, Yamanaka O, Miyamoto T, Kon S, Uede T, Rittling SR, Denhardt DT, Saika S.
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Journal Title
Invest Ophthalmol Vis Sci. 51
Pages: 790-4
Related Report
Peer Reviewed
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[Journal Article] Impaired angiogenic response in the corneas of mice lacking osteopontin.2009
Author(s)
Fujita N, Fujita S, Okada Y, Fujita K, Kitano A, Yamanaka O, Miyamoto T, Kon S, Uede T, Rittling SR, Denhardt DT, Saika S
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Journal Title
Invest Ophthalmol Vis Sci 51(2)
Pages: 790-4
Related Report
Peer Reviewed
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[Journal Article] Epithelial-mesenchymal transition as a therapeutic target for prevention of ocular tissue fibrosis.2008
Author(s)
Saika S, Yamanaka O, Flanders KC, Okada Y, Miyamoto T, Sumioka T, Shirai K, Kitano A, Miyazaki K, Tanaka S, Ikeda K.
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Journal Title
Endocr Metab Immune Disord Drug Targets. 8
Pages: 69-76
Related Report
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[Journal Article] Epithelial-mesenchymal transition as a therapeutic target for prevention of oculartissue fibrosis.2008
Author(s)
Saika S, Yamanaka O, Flanders KC, Okada Y, Miyamoto T, Sumioka T, Shirai K, Kitano A, Miyazaki K, Tanaka S, Ikeda K.
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Journal Title
Endocr Metab Immune Disord Drug Targets 8(1)
Pages: 69-76
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