title: Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5.
abstract: Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance.
authors.affiliation: Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA, UK.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wright
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Berends
authors.forename: David J
authors.initials: DJ
authors.lastname: Flint
authors.forename: Patricia E M
authors.initials: PE
authors.lastname: Martin
mesh_terms: D018929:Cell Culture Techniques; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017630:Connexins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000494:pharmacology*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008962:Models, Theoretical; D009842:Oligopeptides; D009994:Osmolar Concentration; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D017630:Connexins; D007328:Insulin; D018975:Insulin-Like Growth Factor Binding Protein 5; D009842:Oligopeptides; C455880:gap 27 peptide; D005947:Glucose