T-cell factor-4-dependent up-regulation of fibronectin is involved in fibroblast growth factor-2-induced tube formation by endothelial cells.
Deletion of fibronectin or its receptor, alpha(5) integrin, interferes with the formation of a functional circulation in mice. We hypothesized that alpha(5)beta(1) integrin/fibronectin interaction may be involved in differentiation of endothelial cells during angiogenesis. We examined the effect of blocking antibody against alpha(5)beta(1) integrin in fibroblast growth factor-2 (FGF-2)-induced angiogenesis ... by Matrigel plug assay. Although the antibody did not inhibit the recruitment of endothelial cells into plugs, it inhibited organization of lumen-containing capillaries. The antibody also inhibited FGF-2-induced tube formation by murine brain capillary endothelial cells (IBE cells) cultured in type I collagen gels. We previously showed that FGF-2 failed to induce tube formation by IBE cells expressing kinase-dead c-Fyn (KDFyn cells). Association with beta-catenin enhances the transcriptional activity of T-cell factor-4 (TCF-4), which up-regulates the expression of fibronectin. FGF-2 induced association of beta-catenin with TCF-4 and up-regulation of fibronectin in IBE cells, but not in KDFyn cells. Expression of mutant TCF-4, which does not associate with beta-catenin, inhibited FGF-2-induced tube formation and expression of fibronectin in IBE cells. FGF-2-induced tyrosine phosphorylation of beta-catenin, and association with TCF-4 was increased in IBE cells, but not in KDFyn cells. Taken together, interaction of alpha(5)beta(1) integrin and fibronectin is involved in FGF-2-induced tube formation by endothelial cells and up-regulation of fibronectin through TCF-4 seemed to be involved in this process.
Mesh Terms:
Animals, Antibodies, Cell Line, Collagen, Cytoskeletal Proteins, Drug Combinations, Endothelial Cells, Fibroblast Growth Factor 2, Fibronectins, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Integrin alpha5beta1, Laminin, Mice, Oligopeptides, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Kinase Inhibitors, Proteoglycans, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Up-Regulation, beta Catenin, src-Family Kinases
Animals, Antibodies, Cell Line, Collagen, Cytoskeletal Proteins, Drug Combinations, Endothelial Cells, Fibroblast Growth Factor 2, Fibronectins, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Integrin alpha5beta1, Laminin, Mice, Oligopeptides, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Kinase Inhibitors, Proteoglycans, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Up-Regulation, beta Catenin, src-Family Kinases
J. Cell. Biochem.
Date: Mar. 01, 2005
PubMed ID: 15578569
View in: Pubmed Google Scholar
Download Curated Data For This Publication
223189
Switch View:
- Interactions 4