Hsa-miR-6727-5p contributes to the impact of high density lipoprotein on fibroblast wound healing in vitro

Chronic, non-healing wounds are a significant cause of global morbidity and mortality, and strategies to improve delayed wound closure represent an unmet clinical need. High density lipoproteins (HDL) can enhance wound healing, but exploitation of this finding is challenging due to the complexity and unstability of this heterogeneous lipoprotein class. The responsiveness of primary human neonatal keratinocytes, and neonatal and human dermal fibroblasts to HDL was confirmed by cholesterol efflux, but promotion of ‘scrape’ wound healing occurred only in primary human neonatal and adult fibroblasts (HDF). Treatment of human fibroblasts with HDL induced multiple changes in the expression of small non-coding microRNA sequences, determined by microchip array, including hsa-miR-6727-5p. Intriguingly, levels of hsa-miR-6727-5p increased in neonatal human fibroblasts (HDFn), but decreased in adult human fibroblasts (HDFa), after exposure to HDL; delivery of a hsa-6727-5p mimic also elicited repression of different target genes in HDFn (ZNF584) and HDFa (EDEM3, KRAS) while promotion of wound closure was observed in the presence of a hsa-6727-5p mimic in HDFn and by an inhibitor in HDFa. We conclude that treatment with HDL exerts distinct effects on the expression of hsa-miR-6727-5p in adult and neonatal fibroblasts; this sequence also plays differential roles in wound healing, but cannot replicate the myriad effects of HDL itself in these cell types.