title: Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has3.
abstract: Hyaluronan (HA) is an abundant matrix molecule, the function of which in the skin remains to be fully defined. To explore the roles of HA in cutaneous injury responses, double-knockout mice (abbreviated as Has1/3 null) that lack two HA synthase enzymes (Has1 and Has3), but still express functional Has2, were used in two types of experiments: (i) application of 12-O-tetradecanoylphorbol-13-acetate (TPA) and (ii) full-thickness wounding of the skin. Uninjured Has1/3-null mice were phenotypically normal. However, after TPA, the accumulation of HA that normally occurs in wild-type epidermis was blunted in Has1/3-null epidermis. In excisional wound-healing experiments, wound closure was significantly faster in Has1/3 null than in wild-type mice. Coincident with this abnormal wound healing, a marked decrease in epidermal and dermal HA and a marked increase in neutrophil efflux from cutaneous blood vessels were observed in Has1/3-null skin relative to wild-type skin. Has1/3-null wounds displayed an earlier onset of myofibroblast differentiation. In summary, selective loss of Has1 and Has3 leads to a proinflammatory milieu that favors recruitment of neutrophils and other inflammation-related changes in the dermis.
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Mack
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Feldman
authors.forename: Naoki
authors.initials: N
authors.lastname: Itano
authors.forename: Koji
authors.initials: K
authors.lastname: Kimata
authors.forename: Mark
authors.initials: M
authors.lastname: Lauer
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.forename: Edward V
authors.initials: EV
authors.lastname: Maytin
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003872:Dermatitis / Q000276:immunology / Q000503:physiopathology*; D020405:Dermis / Q000187:drug effects / Q000276:immunology / Q000293:injuries; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000293:injuries; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000076002:Hyaluronan Synthases; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D002273:Carcinogens; D014453:Glucuronosyltransferase; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases; D013755:Tetradecanoylphorbol Acetate