Angiogenesis Is Not Impaired in Connective Tissue Growth Factor (CTGF) Knock-out Mice

• DOI: 10.1369/jhc.7a7258.2007
• Publication Date: 2007-07-12T01:46:33Z
• Authors: Esther J. Kuiper; Peggy Roestenberg; Christoph Ehlken; Vincent Lambert; Henny Bloys van T...; Karen M. Lyons; Hans-Jürgen T. Ag...; Jean-Marie Rakic; Ingeborg Klaassen; Cornelis J. F. Va...; Roel Goldschmeding; Reinier O. Schlin...
• Keywords: Mice, Knockout; Vascular Endothelial Growth Factor A; 0303 health sciences; Neovascularization, Pathologic; Lasers; NCMLS 2: Metabolism, transport and motion; Connective Tissue Growth Factor; In Vitro Techniques; Embryo, Mammalian; Bone and Bones; Choroidal Neovascularization; Immediate-Early Proteins; 3. Good health; Oxygen; Mice; 03 medical and health sciences; UMCN 5.3: Cellular energy metabolism; Animals, Newborn; Retinal Diseases; Animals; Intercellular Signaling Peptides and Proteins; IGMD 8: Mitochondrial medicine

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.