Modulating connexin (Cx) mediated communication (CMC) increases wound-healing. The effects of Gap27, a connexin mimetic peptide, on CMC and cell migration of human dermal fibroblasts and epidermal keratinocytes in euglycaemia/euinsulinaemia or hyperglycaemia/hyperinsulinaemia was examined. Cells were treated with 5.5 mM glucose and 1 nM insulin, or 25 mM glucose and 10 nM insulin. Dye transfer and western blotting measured connexin function and expression; scrape-wound assays assessed cell migration +/- 100 µM Gap27. Hyperglycaemic/hyperinsulinaemic cells showed reduced CMC compared to euglycaemic/euinsulinaemic cells (P<0.05), which Gap27 further reduced (P<0.001). Fibroblast Cx43 protein levels were increased in hyperglycaemia/hyperinsulinaemia. Gap27 increased fibroblast (P<0.01) and keratinocyte (P<0.05) migration. Despite increased Cx43 in hyperglycaemic/hyperinsulinaemic fibroblasts, mimicking raised Cx43 seen at ulcer edges, Gap27 blocked CMC and augmented cell migration in both fibroblasts and keratinocytes. Connexin mimetic peptides can improve cell motility in skin cells exposed to diabetes drivers and have therapeutic potential.
|Publication status||Published - 2011|
- cell–cell communication