Hypoxia upregulates VEGF production in keloid fibroblasts

The etiology of keloid formation is diverse. They are characterized grossly as thick scar tissue that extends beyond the boundaries of the original wo und. Histologically, keloids are composed of excessive collagen with an abn ormally large number of partially or totally occluded microvessels. This oc clusion of keloid microvessels has been hypothesized to contribute to a hyp oxic microenvironment within these pathological scars. Vascular endothelial growth factor (VEGF), a potent endothelial cell mitogen, and proangiogenic cytokine have been implicated in normal and pathological wound healing. Th e purpose of this study was to evaluate the amount of VEGF protein producti on by fibroblast cell lines derived from keloids and normal human dermal sk in in hypoxic compared with normoxic culture conditions. By enzyme-linked i mmunosorbent protein assay, VEGF was increased in both keloid and normal hu man dermal fibroblasts in hypoxia over normoxic controls. There was not, ho wever, a significant difference between upregulation of VEGF protein when c omparing the keloid and normal fibroblast groups. As the result of the data , alternative hypotheses for hypoxia-induced keloid formation were explored : (1) downstream modulation or signal transduction of VEGF, (2) VEGF produc tion from cells other than fibroblasts, (3) the importance of matrix accumu lation stimulated by hypoxia, or (4) increased migration of cells (other th an fibroblasts) specific to keloid biology. These hypotheses may help expla in the possible role of hypoxia in the pathogenesis of keloid formation. Fu ture studies involving in situ hybridization or immunohistochemical analysi s may offer greater insight into the mechanisms underlying keloid formation . Ultimately, our therapeutic goal is the utilization of biomolecular appro aches for the suppression of keloid formation.