title: Role of endogenous insulin gene enhancer protein ISL-1 in angiogenesis.
abstract: To elucidate the role of insulin gene enhancer protein ISL-1 (Islet-1) in angiogenesis and regulation of vascular endothelial growth factor (VEGF) expression in vitro and in vivo.
  
  
  
  siRNA targeting Islet-1 was transfected to human umbilical vein endothelial cell lines (HUVECs). The expression of Islet-1 and VEGF in the cultured cells was measured using real-time PCR and immunoblotting. 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide; thiazolyl blue (MTT) assay was used to analyze the proliferation of HUVECs affected by Islet-1. Wound healing and Transwell assays were conducted to assess the motility of HUVECs. The formation of capillary-like structures was examined using growth factor-reduced Matrigel. siRNA targeting Islet-1 was intravitreally injected into the murine model of oxygen-induced retinopathy (OIR). Retinal neovascularization was evaluated with angiography using fluorescein-labeled dextran and then quantified histologically. Real-time PCR and immunoblotting were used to determine whether local Islet-1 silencing affected the expression of Islet-1 and VEGF in murine retinas.
  
  
  
  The expression of Islet-1 and VEGF in HUVECs was knocked down by siRNA. Reduced endogenous Islet-1 levels in cultured cells greatly inhibited the proliferation, migration, and tube formation in HUVECs in vitro. Retinal neovascularization following injection of Islet-1 siRNA was significantly reduced compared with that of the contralateral control eye. Histological analysis indicated that the neovascular nuclei protruding into the vitreous cavity were decreased. Furthermore, the Islet-1 and VEGF expression levels were downregulated in murine retinas treated with siRNA against Islet-1.
  
  
  
  Reducing the expression of endogenous Islet-1 inhibits proliferation, migration, and tube formation in vascular endothelial cells in vitro and suppresses retinal angiogenesis in vivo.Endogenous Islet-1 regulates angiogenesis via VEGF.
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Xiong
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Yan-Xiu
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Hui-Zhuo
authors.initials: HZ
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Zhen-Kai
authors.initials: ZK
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, P.R.China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Xia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen; D004195:Disease Models, Animal; D004338:Drug Combinations; D005451:Fluorescein Angiography; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015151:Immunoblotting; D060850:LIM-Homeodomain Proteins / Q000502:physiology*; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015861:Retinal Neovascularization / Q000175:diagnosis / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D060850:LIM-Homeodomain Proteins; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C063843:insulin gene enhancer binding protein Isl-1; C059485:matrigel; D003094:Collagen