title: Deletion of the homeobox gene PRX-2 affects fetal but not adult fibroblast wound healing responses.
abstract: The phenotype of fibroblasts repopulating experimental wounds in vivo has been shown to influence both wound healing responses and clinical outcome. Recent studies have demonstrated that the human homeobox gene PRX-2 is strongly upregulated in fibroblasts within fetal, but not adult, mesenchymal tissues during healing. Differential homeobox gene expression by fibroblasts may therefore be important in mediating the scarless healing exhibited in early fetal wounds. RNase protection analysis demonstrated that murine Prx-2 expression was involved in fetal but not adult wound healing responses in vitro. Using fibroblasts established from homozygous mutant (Prx-2-/-) and wild-type (Prx-2+/+) murine skin tissues it was demonstrated that Prx-2 affected a number of fetal fibroblastic responses believed to be important in mediating scarless healing in vivo; namely cellular proliferation, extracellular matrix reorganization, and matrix metalloproteinase 2 and hyaluronic acid production. These data demonstrate how Prx-2 may contribute to the regulation of fetal, but not adult, fibroblasts and ultimately the wound healing phenotype. This study provides further evidence for the importance of homeobox transcription factors in the regulation of scarless wound healing. A further understanding of these processes will, it is hoped, enable the targeting of specific therapies in wound healing, both to effect scarless healing and to stimulate healing in chronic, nonhealing wounds such as venous leg ulcers.
authors.affiliation: Department of Oral Surgery, Medicine, and Pathology, University of Wales College of Medicine, Cardiff, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: White
authors.forename: David W
authors.initials: DW
authors.lastname: Thomas
authors.forename: Steven
authors.initials: S
authors.lastname: Fong
authors.forename: Eric
authors.initials: E
authors.lastname: Stelnicki
authors.forename: Fritz
authors.initials: F
authors.lastname: Meijlink
authors.forename: Corey
authors.initials: C
authors.lastname: Largman
authors.forename: Phil
authors.initials: P
authors.lastname: Stephens
mesh_terms: D000818:Animals; D002455:Cell Division; D005109:Extracellular Matrix / Q000502:physiology; D005333:Fetus / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006820:Hyaluronic Acid / Q000378:metabolism; D008666:Metalloendopeptidases / Q000032:analysis; D051379:Mice; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C115469:Prrx2 protein, mouse; D019716:Tissue Inhibitor of Metalloproteinase-2; D006820:Hyaluronic Acid; D008666:Metalloendopeptidases