Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.

Abstract

Abstract. Human umbilical vein endothelial (HUVE) cells have been previously reported to express the genes for the A and B chains of PDGF and to secrete PDGF-related factors into culture media. Antihuman PDGF IgG affinity chromatography was used to purify PDGF-related activity from HUVE cell-conditioned media . Immunoblot analysis of the affinity-purified proteins with anti-PDGF IgG and antibodies specific for the A or B chain peptides of PDGF combined with chemotactic and mitogenic assays revealed that the major PDGF immunorelated molecule secreted by HUVE cells is a monomer of ti 36-38 kD and that

Human CYR61-mediated enhancement of bFGF-induced DNA synthesis in human umbilical vein endothelial cells

“…CYR61 is a member of a family of structurally conserved proteins that includes the connective tissue growth factor and the proto-oncoprotein Nov (Joliot et al, 1992;Bradham et al, 1991). CYR61 is encoded by an immediate-early gene and is synthesized upon stimulation by serum growth factors, including bFGF (Lau and Nathans, 1987;O'Brien et al, 1990).…”

“…Both CYR61 and the structurally related CTGF are induced in dermal ®broblasts during wound healing (Igarashi et al, 1993;Latinkic, 1994). Since both CYR61 and CTGF are chemotactic for ®broblasts, and CTGF is mitogenic (Bradham et al, 1991) whereas CYR61 enhances bFGF-induced DNA synthesis (Figure 3), these protein may function to enhance both migration and proliferation of dermal ®broblasts for wound repair.…”

“…RNA samples were analysed by electrophoretic separation in formaldehyde-agarose gels followed by transfer to nylon ®lters. Blots were hybridized with 32 P-labeled cDNA probes of hCYR61, CTGF (Bradham et al, 1991), novH (Martinerie et al, 1994) or b-actin.…”

“…These secreted, cysteine-rich proteins have been named members of the`CCN family' (for Cyr61/Cef10, CTGF/Fisp12, and Nov; Bork, 1993) and include at least three distinct members: cyr61/cef10 (Simmons et al, 1989;O'Brien et al, 1990), CTGF/®sp12 (Bradham et al, 1991;Ryseck et al, 1991) and nov Joliot et al, 1992). Members of this protein family share a high level of sequence homology, including complete conservation of 38 cysteine residues in their secreted portion.…”

“…cef10, the chicken ortholog of cyr61, was also cloned as a growth factor-and v-src-inducible immediate-early gene (Simmons et al, 1989). ®sp12 was later found to be the mouse homolog of the human connective tissue growth factor (CTGF; Bradham et al, 1991), which was identi®ed by virtue of its mitogenic activity in human umbilical vein endothelial cells (HUVECs; Bradham et al, 1991). CTGF is also mitogenic for ®broblasts in culture and is expressed in dermal ®broblasts during wound healing (Igarashi et al, 1993;Frazier et al, 1996).…”