Development of a novel treatment strategy based on the oles of sphingosine-1- phosphate in EMT-related ocular tissue fibrosis
Project/Area Number |
17K11464
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | Wakayama Medical University |
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) |
住岡 孝吉 和歌山県立医科大学, 医学部, 准教授 (40433362)
田中 才一 和歌山県立医科大学, 医学部, 准教授 (60316106)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | スフィンゴシン・1リン酸 / 水晶体上皮細胞 / 角膜内皮 / 上皮—間葉系移行 / 線維・瘢痕化 / 後発白内障 / 創傷治癒 / マウス / 水晶体上皮 / 上皮ー間葉系移行 / 筋線維芽細胞 / スフィンゴシン・1リン酸受容体 / トランスフォーミング成長因子 / 角膜創傷治癒 / スフィンゴシンー1ーリン酸受容体 / 上皮-間葉系移行 / 炎症 / スフィンゴシン・1リン酸受容体3型 / スフィンゴシン・1リン酸受容体2型 / 増殖硝子体網膜症 |
Outline of Final Research Achievements |
In this study, we focused on whether the sphingosine monophosphate (S1P) signal, a cell membrane sphingolipid metabolite, is involved in the regulation of epithelial-mesenchymal transition in tissue fibers and scarring. As a model of aftercataract, EMT of lens epithelial cells in lens perforation trauma was examined. In an S1P receptor type 3 deficient mouse, the initiation of smooth muscle actin expression, an EMT marker, was delayed. The endothelium-mesenchymal transition, EnMT, of the corneal endothelium was used to investigate fibrosis of the endothelial surface. When mouse corneal alkaline trauma was created with 1N NaOH, fibrotic lesions were formed on the endothelial surface by EnMT of the endothelial cells. The degree of corneal endothelium EnMT and fibrosis were similar to each other between wild-type and S1P3 receptor-deficient mice.
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Academic Significance and Societal Importance of the Research Achievements |
臨床的に水晶体上皮細胞のEMTは白内障手術で挿入された眼内レンズ周囲の残存水晶体嚢の線維性混濁(後発白内障)による視力低下や眼内レンズの変位の原因である。今研究では後発白内障の発症機序にS1Pシグナルが関与していることが明らかとなった。S1Pシグナル阻害による予防効果が示唆された。一方、角膜内皮細胞のEnMTによる線維性病変の形成は、高度の角膜炎症疾患や炎症に合併する。同病変の形成にはS1PR3シグナルの関与が少ないことが示唆された。
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4.2019
Author(s)
Okada Y, Sumioka T, Ichikawa K, Sano H, Nambu A, Kobayashi K, Uchida K, Suzuki Y, Tominaga M, Reinach PS, Hirai SI, Jester JV, Miyajima M, Shirai K, Iwanishi H, Kao WW, Liu CY, Saika S.
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Journal Title
Lab Invest.
Volume: 99(2)
Issue: 2
Pages: 210-230
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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