網膜色素上皮細胞における上皮間葉移行関連転写因子の探索

寻找与视网膜色素上皮细胞上皮间质转化相关的转录因子

• 批准号: 22791644
• 负责人: 村田 美幸
• 金额: $ 2.5万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791644/
• 关键词: 眼科学; 網膜; 上皮間葉移行; 加齢黄斑変性

加齢黄斑変性(AMD)の病型の一つ、滲出型AMDの病態を特徴づける脈絡膜新生血管(CNV)はその終末期病態として線維化をきたし、視力障害の原因となる。近年,組織の線維化においてEpithelial-Mesenchymal Transition(上皮間葉移行:EMT)が着目されているが、ヒトCNV組織検体を用いた我々の検討結果ではEMTを制御する転写因子の一つSnailがヒトCNV中の網膜色素上皮細胞(RPE)に高発現しており,線維化をきたしている組織ほどその陽性率が高いことが明らかとなった。この結果はCNV中に含まれるRPEがEMTを生じていること、EMTの転写因子SnailがCNVの線維化に関与する可能性を示唆していた。本研究では、培養ヒトRPE細胞株ARPE19を用いたin vitro実験系により、EMT関連転写因子snailの制御機構を解析した。CNV組織において発現が確認されている各種サイトカイン(transforming growth factor (TGF)-b, tumor-necrosis factor (TNF)-a, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF)など)を用いてARPE19細胞を刺激したところ、TGF-b刺激による転写因子Snailの発現増加がRT-PCRおよび免疫組織染色によって確認された。本結果は、ヒトCNV中に存在するTGF-bがEMT転写因子Snailの発現を誘導し、CNV組織においてRPEにEMT変化を惹起するということを示唆していた。

In addition to macular disease (AMD) disease type 1 and type AMD, the special symptoms of macular disease, membrane neovascularization (CNV), the terminal stage of disease, the cause of stress disorder, and the cause of stress disorder. In recent years, tissue maintenance Epithelial-Mesenchymal Transition (epithelial migration: EMT) aims to improve the response rate of Snail pigment epithelial cells (RPE) in CNV. In recent years, tissue tissue migration (epithelial cell migration: EMT) has been used to control writing factors such as the expression of membrane pigment epithelium (RPE) in CNV, and the sensitivity of tissue phenotype. The results of the CNV show that there are some errors in the CNV, such as RPE EMT, EMT write factors, Snail, CNV, maintenance, and possibility. In this study, the RPE cell line ARPE19 was used to analyze the factors of snail, which were written by the in vitro strain and the EMT cell line. The CNV organization confirmed that all kinds of expression genes (transforming growth factor (TGF)-b, tumor-necrosis factor (TNF)-a, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) genes) were stimulated by ARPE19 cells, and the expression factor Snail was stimulated by TGF-b. The expression was confirmed by RT-PCR immuno-histochemical staining. This result shows that there are some TGF-b EMT writing factors in the CNV, such as the Snail implementation guide, and the CNV organization response to RPE EMT changes, which causes symptoms to be detected.