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.
Kanda
Shigeru
S
Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. shigeruk@net.nagasaki-u.ac.jp
Miyata
Yasuyoshi
Y
Kanetake
Hiroshi
H
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D003094:Collagen; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D007797:Laminin; D051379:Mice; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D005353:Fibronectins; D039081:Integrin alpha5beta1; D007797:Laminin; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D019000:Phosphotyrosine; D003094:Collagen; C049554:glycyl-arginyl-glycyl-aspartyl-serine; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3