Connective Tissue Growth Factor Induces the Proliferation, Migration, and Tube Formation of Vascular Endothelial Cells In Vitro, and Angiogenesis In Vivo

Abstract

Connective tissue growth factor (CTGF) is a novel cysteine-rich, secreted protein. Recently, we found that inhibition of the endogenous expression of CTGF by its antisense oligonucleotide and antisense RNA suppresses the proliferation and migration of vascular endothelial cells. In the present study, the following observations demonstrated the angiogenic function of CTGF in vitro and in vivo: (i) purified recombinant CTGF (rCTGF) promoted the adhesion, proliferation and migration of vascular endothelial cells in a dose-dependent manner under serum-free conditions, and these effects were inhibited by anti-CTGF antibodies; (ii) rCTGF markedly induced the tube formation of vascular endothelial cells, and this effect was stronger than that of basic fibroblast growth factor or vascular endothelial growth factor; (iii) application of rCTGF to the chicken chorioallantoic membrane resulted in a gross angiogenic response, and this effect was also inhibited by anti-CTGF antibodies. (iv) rCTGF injected with collagen gel into the backs of mice induced strong angiogenesis in vivo. These findings indicate that CTGF is a novel, potent angiogenesis factor which functions in multi-stages in this process.

Profiling of genes which are differentially expressed in mouse liver in response to adenoviral vectors and delivered genes

“…[17][18][19][20] Increases in expression of u-PAR1, laminin receptor and BMP-1 are consistent with the importance of CTGF and TGF␤1 in tissue repair and remodeling. Bone morphogenetic protein (BMP-1) is identical to procollagen C-proteinase, which cleaves the COOH-propeptides of procollagens I, II and III to yield to major fibrous components of vertebrate extracellular matrix.…”

“…It has been shown that the expression of u-PAR is required for angiogenesis 23 and both TGF␤1 and CTGF genes are known to induce angiogenesis. 19,20 The observation that u-PAR is expressed in fibrotic fibroblasts and is responsible for cell migration and chemtotaxis, 24,25 which are also known functions of CTGF and TGF␤1, indicates that u-PAR may be induced by CTGF and TGF␤1 in wound repair.…”

Physical interaction of CCN2 with diverse growth factors involved in chondrocyte differentiation during endochondral ossification

“…1998;Shimo et al 1999;Kubota and Takigawa 2007a, b. )Similarly,as an angiogenetic factor, VEGF is essential for establishing epiphyseal vascularization (Maes et al 2004).…”

Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: Similarities to retroviral RNA-protein interactions

“…It is a mitogenic and chemotactic cytokine for ®broblasts (Kothapalli et al, 1997), which provides a rationale for the active role(s) of CTGF in wound healing (Igarashi et al, 1993). Angiogenic activities of CTGF have been disclosed as well by a few independent research groups including ours (Babic et al, 1999;Shimo et al, 1999). The complex and integrated functionality of CTGF is also well-represented in its comprehensive roles in endochondral ossi®cation, most of which have been uncovered in our series of recent studies (Nakanishi et al, 1997;Nishida et al, 1998).…”