title: Hypoxia upregulates VEGF production in keloid fibroblasts.
abstract: The etiology of keloid formation is diverse. They are characterized grossly as thick scar tissue that extends beyond the boundaries of the original wound. Histologically, keloids are composed of excessive collagen with an abnormally large number of partially or totally occluded microvessels. This occlusion of keloid microvessels has been hypothesized to contribute to a hypoxic 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. The purpose of this study was to evaluate the amount of VEGF protein production by fibroblast cell lines derived from keloids and normal human dermal skin in hypoxic compared with normoxic culture conditions. By enzyme-linked immunosorbent protein assay, VEGF was increased in both keloid and normal human dermal fibroblasts in hypoxia over normoxic controls. There was not, however, a significant difference between upregulation of VEGF protein when comparing 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 production from cells other than fibroblasts, (3) the importance of matrix accumulation stimulated by hypoxia, or (4) increased migration of cells (other than fibroblasts) specific to keloid biology. These hypotheses may help explain the possible role of hypoxia in the pathogenesis of keloid formation. Future studies involving in situ hybridization or immunohistochemical analysis may offer greater insight into the mechanisms underlying keloid formation. Ultimately, our therapeutic goal is the utilization of biomolecular approaches for the suppression of keloid formation.
authors.affiliation: Department of Surgery, New York University School of Medicine, NY 10016, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Steinbrech
authors.forename: B J
authors.initials: BJ
authors.lastname: Mehrara
authors.forename: D
authors.initials: D
authors.lastname: Chau
authors.forename: N M
authors.initials: NM
authors.lastname: Rowe
authors.forename: G
authors.initials: G
authors.lastname: Chin
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.forename: P B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: G K
authors.initials: GK
authors.lastname: Gittes
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D016228:Endothelial Growth Factors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007627:Keloid / Q000473:pathology / Q000503:physiopathology*; D008222:Lymphokines / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors