Activation of AP-1 and SP1 correlates with wound growth factor gene expression in glucan-treated human fibroblasts.
Glucan is a natural product immunomodulator that has been reported to enhance early wound repair. The mechanism of glucan-stimulated wound repair was thought to be indirect via macrophage release of wound growth factors. However, recent data indicate that there are glucan-specific receptors on human fibroblasts that can modulate cellular function following interaction with the glucan ligand. In this study we examined the effect of glucan on activation of the transcription factors activator protein-1 (AP-1) and specificity protein-1 (Sp1) in normal human dermal fibroblasts. AP-1 and Sp1 are involved in the regulation of cytokine and procollagen genes. In addition, we evaluated the effect of glucan on wound growth factor and vascular endothelial growth factor (VEGF) mRNA expression in primary cultures of normal human dermal fibroblasts. Glucan (1 microg/ml) stimulated fibroblast AP-1 and Sp1 activation in a time-dependent manner, although the temporal kinetics varied between the two transcription factors. AP-1 binding activity was increased (p<0.05) at early time intervals (1, 2, 4, 8 and 12 h), while Sp1 nuclear binding activity was increased (p<0.05) at later time intervals (12, 24, 36 and 48 h). Glucan (1 microg/ml) stimulated fibroblast expression of neurotrophin 3 (NT-3), platelet derived growth factor A (PDGF-A), platelet derived growth factor B (PDGF-B), fibroblast growth factor acidic (aFGF), fibroblast growth factor basic (bFGF), transforming growth factor alpha (TGFalpha), transforming growth factor beta (TGFbeta) and VEGF mRNA at 8 h.
D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005936:Glucans / Q000494:pharmacology*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics*
D016228:Endothelial Growth Factors; D005936:Glucans; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors