title: [RhoJ signaling pathway in retinal angiogenesis: promising targets for novel anti-angiogenic therapy].
abstract: In quiescent retinal vessels, adjacent endothelial cells (ECs) form a tightly sealed junction, leading to maintenance of vascular integrity. By contrast, during pathological angiogenesis in diabetic retinopathy and age-related macular degeneration, vascular endothelial growth factor (VEGF) activates intracellular signaling pathways in ECs, resulting in the dissociation of cell-cell adhesions and induction of EC migration. To inhibit undesirable angiogenesis, it would be clinically beneficial to manipulate intracellular signals that control migratory behavior of ECs. Here we show that the small GTPase RhoJ is expressed predominantly in angiogenic ECs, and regulates cell motility through cytoskeletal rearrangement. We also found that Arhgef15, an EC-specific guanine nucleotide exchange factor, inactivates RhoJ downstream of VEGF signals, thereby promoting retinal vascular growth. These signaling molecules can be potential drug targets for novel antiangiogenic therapy.
authors.affiliation: Division of Vascular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. yoko0812@med.kobe-u.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012171:Retinal Vessels / Q000502:physiology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: C578514:ARHGEF15 protein, human; D020662:Guanine Nucleotide Exchange Factors; D042461:Vascular Endothelial Growth Factor A; C417188:RHOJ protein, human; D020741:rho GTP-Binding Proteins