title: Elevated vascular endothelial growth factor in keloids: relevance to tissue fibrosis.
abstract: Excessive scar or keloid shares common features of a benign dermal growth. Yet, in contrast to malignant tumor, a keloid does not expand beyond the dermis. What triggers the continuing growth of a benign lesion? Deficient or overabundant levels of vascular endothelial growth factor have been reported to contribute to impaired or excessive wound healing. Although numerous studies have examined the pathophysiology of impaired wounds, little information has been provided on mechanisms of exuberant healing. The molecular basis of keloid formation is governed by the interplay of cellular signaling pathways, specific target gene activation, and the nature of the microenvironment. Recent works have demonstrated an accumulation of hypoxia-inducible factor-1alpha protein in freshly biopsied keloid tissues, thus providing first evidence that a local state of hypoxia exists in keloids. Our findings and the findings of others support at least two plausible mechanisms implicated in the development of fibrotic wounds, a state of ongoing fibroplasia or inflammation and an excessive accumulation of extracellular matrix. This article will review recent works examining the potential role of vascular endothelial growth factor in keloid pathogenesis with particular focus on its involvement in the two proposed pathological processes, a prolonged inflammation and an altered balance in extracellular matrix metabolism.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Charles R. Drew University of Medicine and Science, University of California, Los Angeles, Calif., USA. anle@cdrewu.edu
authors.forename: Anh D
authors.initials: AD
authors.lastname: Le
authors.forename: Qunzhou
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yidi
authors.initials: Y
authors.lastname: Wu
authors.forename: Diana V
authors.initials: DV
authors.lastname: Messadi
authors.forename: Anita
authors.initials: A
authors.lastname: Akhondzadeh
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Nguyen
authors.forename: Tara L
authors.initials: TL
authors.lastname: Aghaloo
authors.forename: A Paul
authors.initials: AP
authors.lastname: Kelly
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bertolami
mesh_terms: D004268:DNA-Binding Proteins / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A