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: Catherine S Wright, Rebecca F Berends, David J Flint, Patricia E M Martin
• Journal: Experimental cell research (Exp Cell Res) Vol. 319 Issue 4 Pg. 390-401 (Feb 15 2013) ISSN: 1090-2422 [Electronic] United States
• PMID: 23262023 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Connexins
• Insulin
• Insulin-Like Growth Factor Binding Protein 5
• Oligopeptides
• gap 27 peptide
• Glucose

Topics

• Cell Culture Techniques
• Cell Migration Assays
• Cell Movement (drug effects, physiology)
• Cells, Cultured
• Connexins (pharmacology)
• Dose-Response Relationship, Drug
• Glucose (pharmacology)
• Humans
• Infant, Newborn
• Insulin (pharmacology)
• Insulin-Like Growth Factor Binding Protein 5 (pharmacology)
• Keratinocytes (cytology, drug effects)
• Models, Theoretical
• Oligopeptides
• Osmolar Concentration
• Skin Physiological Phenomena (drug effects)
• Up-Regulation (drug effects)
• Wound Healing (drug effects)