arhgef15 promotes retinal angiogenesis by mediating vegf-induced cdc42 activation and potentiating rhoj inactivation in endothelial cellsarhgef15促进视网膜血管生成通过调解vegf-induced cdc42激活和增效rhoj在内皮细胞失活.pdf

Arhgef15 Promotes Retinal Angiogenesis by Mediating VEGF-Induced Cdc42 Activation and Potentiating RhoJ Inactivation in Endothelial Cells 1,2. 1,3,4. 5 1 1 Sentaro Kusuhara , Yoko Fukushima , Shigetomo Fukuhara , Lars Martin Jakt , Mitsuhiro Okada , 1 3 4 2 3 5 Yuri Shimizu , Masayuki Hata , Kohji Nishida , Akira Negi , Masanori Hirashima , Naoki Mochizuki , Shin-Ichi Nishikawa1, Akiyoshi Uemura1,2,3* 1 Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan, 2 Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan, 3 Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan, 4 Department of Ophthalmology, Osaka University Medical School, Osaka, Japan, 5 Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan Abstract Background: Drugs inhibiting vascular endothelial growth factor (VEGF) signaling are globally administered to suppress deregulated angiogenesis in a variety of eye diseases. However, anti-VEGF therapy potentially affects the normal functions of retinal neurons and glias which constitutively express VEGF receptor 2. Thus, it is desirable to identify novel drug targets which are exclusively expressed in endothelial cells (ECs). Here we attempted to identify an EC-specific Rho guanine nucleotide exchange factor (GEF) and evaluate its role in retinal angiogenesis. Methodology/Principal Findings: By exploiting fluorescence-activated cell sorting