title: Angiogenesis is not impaired in connective tissue growth factor (CTGF) knock-out mice.
abstract: 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.
authors.affiliation: Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Kuiper
authors.forename: Peggy
authors.initials: P
authors.lastname: Roestenberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Ehlken
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Henny Bloys
authors.initials: HB
authors.lastname: van Treslong-de Groot
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lyons
authors.forename: Hans-Jürgen T
authors.initials: HJ
authors.lastname: Agostini
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klaassen
authors.forename: Cornelis J F
authors.initials: CJ
authors.lastname: Van Noorden
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D055513:Connective Tissue Growth Factor; D004622:Embryo, Mammalian / Q000098:blood supply; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007834:Lasers; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen; D012164:Retinal Diseases / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D010100:Oxygen