Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

Catherine S Wright, Rebecca F Berends, David J Flint, Patricia E M Martin

Research output: Contribution to journalArticle

15 Citations (Scopus)

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-1 enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-1 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.
Original languageEnglish
Pages (from-to)390-401
Number of pages12
JournalExperimental Cell Research
Volume319
Issue number4
Early online date20 Dec 2012
DOIs
Publication statusPublished - 15 Feb 2013

Keywords

  • connexin
  • peptide
  • keratinocytes
  • skin
  • wound
  • IGF

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