Regulation of connective tissue growth factor gene expression in retinal vascular endothelial cells by angiogenic growth factors

Background: Connective tissue growth factor (CTGF) is a novel, cysteine-ric h secreted protein, which is implicated in fibrotic disorders and atheroscl erosis. To elucidate the role of CTGF in fibrovascular proliferative retino pathy, we investigated the regulation of CTGF gene expression in a cell lin e of retinal vascular endothelial cells (RVEC) stimulated with fetal calf s erum (FCS) and angiogenic growth factors, including vascular endothelial gr owth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BE (PDGF-BB), endothelial growth factor (EGF), transforming growth factor-beta1 and -beta3 (TGF-beta1, TGF-beta3), and insulin-like gro wth factor-I (IGF-I). Methods: RVEC derived from Macaca mulatta (CRL-1780; ATCC) were stimulated with 10% FCS as well as with VEGF, bFGF, PDGF-BB, TGF -beta1, TGF-beta3. EGF, or IGF-I. Time-dependent CTGF gene expression was a ssessed by northern blot analysis. Results: FCS, TGF-beta1, TGF-beta3, bFGF and EGF induced an upregulation of CTGF gene expression in RVEC in a time- dependent manner. Highest expression was induced with TGF-beta1. No respons e on CTGF gene expression could be detected to VEGF, PDGF-BB, or IGF-I. Con clusion: The present study demonstrates for the first time that CTGF mRNA i s expressed at high levels in RVEC, and that the level of the temporal patt ern of its expression is differentially regulated by angiogenic growth fact ors, indicating a significant role of CTGF in the pathological course of un controlled retinal angiogenesis.