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doi:10.1369/jhc.7A7258.2007
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Volume 55 (11): 1139-1147, 2007
Copyright ©The Histochemical Society, Inc.
Angiogenesis Is Not Impaired in Connective Tissue Growth Factor (CTGF) Knock-out Mice
Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (EJK,IK,CJFVN,ROS); Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands (PR,RG); Department of Ophthalmology, University of Freiburg, Freiburg, Germany (CE,H-JTA); Laboratory of Tumor and Development Biology and Department of Ophthalmology, University Hospital Liège, Sart Tilman, Liège, Belgium (VL,J-MR); Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands (HBvT-dG); and Department of Orthopaedic Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California (KML)
Correspondence to: Dr. R.O. Schlingemann, Department of Ophthalmology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail: r.schlingemann{at}amc.uva.nl
Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and subsequent fibrosis are the main causes of blindness in conditions such as diabetic retinopathy. We have applied three different models of angiogenesis to homozygous CTGF–/– and heterozygous CTGF+/– mice to establish involvement of CTGF in neovascularization. CTGF–/– mice die around birth. Therefore, embryonic CTGF–/–, CTGF+/–, and CTGF+/+ bone explants were used to study in vitro angiogenesis, and neonatal and mature CTGF+/– and CTGF+/+ mice were used in models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Angiogenesis in vitro was independent of the CTGF genotype in both the presence and the absence of VEGF. Oxygen-induced vascular pathology in the retina, as determined semi-quantitatively, and laser-induced choroidal neovascularization, as determined quantitatively, were also not affected by the CTGF genotype. Our data show that downregulation of CTGF levels does not affect neovascularization, indicating distinct roles of VEGF and CTGF in angiogenesis and fibrosis in eye conditions. (J Histochem Cytochem 55:1139–1147, 2007)
Key Words: CTGF • VEGF • diabetic retinopathy • angiogenesis • fibrosis • angio-fibrotic switch • vitreous
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