Yes-associated protein promotes endothelial-tomesenchymal transition of endothelial cells in choroidal neovascularization fibrosis

作     者：Rong Zou Yi-Fan Feng Ya-Hui Xu Min-Qian Shen Xi Zhang Yuan-Zhi Yuan 

作者机构：Department of OphthalmologyZhongshan HospitalFudan UniversityShanghaiChina Department of OphthalmologyXiamen BranchZhongshan HospitalFudan UniversityXiamenFujian ProvinceChina 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2022年第15卷第5期

页      面：701-710页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：National Natural Science Foundation of China(No.81970817 No.81873680) 

主　　题：endothelial-to-mesenchymal transition Yes-associated protein hypoxia-inducible factor-1α choroidal neovascularization age-related macular degeneration 

摘      要：AIM:To reveal whether and how Yes-associated protein(YAP)promotes the occurrence of subretinal fibrosis in agerelated macular degeneration(AMD).METHODS:Cobalt chloride(Co Cl2)was used in primary human umbilical vein endothelial cells(HUVECs)to induce hypoxia in ***-week-old male C57 BL/6 J mice weighing 19-25 g were used for a choroidal neovascularization(CNV)model induced by laser photocoagulation in *** levels of YAP,phosphorylated YAP,mesenchymal markers[αsmooth muscle actin(α-SMA),vimentin,and Snail],and endothelial cell markers(CD31 and zonula occludens 1)were measured by Western blotting,quantitative real-time PCR,and immunofluorescence *** molecules YC-1(Lificiguat,a specific inhibitor of hypoxia-inducible factor 1α),CA3(CIL56,an inhibitor of YAP),and XMU-MP-1(an inhibitor of Hippo kinase MST1/2,which activates YAP)were used to explore the underlying ***:Co Cl2 increased expression of mesenchymal markers,decreased expression of endothelial cell markers,and enhanced the ability of primary HUVECs to proliferate and ***-1 suppressed hypoxia-induced endothelialto-mesenchymal transition(End MT).Moreover,hypoxia promoted total expression,inhibited phosphorylation,and enhanced the transcriptional activity of ***-MP-1 enhanced hypoxia-induced End MT,whereas CA3 elicited the opposite *** of YAP,α-SMA,and vimentin were upregulated in the laser-induced CNV ***,silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these ***:The findings reveal a critical role of the hypoxia-inducible factor-1α(HIF-1α)/YAP signaling axis in End MT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.