Homo sapiens (Hsa)-microRNA(miR)-6727-5p contributes to the impact of high density lipoproteins on fibroblast wound healing in vitro

Khaled Mohammed Bastaki, Jamie Maurice Roy Tarlton, Richard James Lightbody, Annette Graham*, Patricia Esther Martin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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 instability of these heterogeneous lipoproteins. The responsiveness of primary human neonatal keratinocytes, and neonatal and human dermal fibroblasts (HDF) to HDL was confirmed by cholesterol efflux, but promotion of ‘scrape’ wound healing occurred only in primary human neonatal (HDFn) and adult fibroblasts (HDFa). 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 HDFn, but decreased in HDFa, after exposure to HDL. Delivery of a hsa-miR-6727-5p mimic elicited repression of different target genes in HDFn (ZNF584) and HDFa (EDEM3, KRAS), and promoted wound closure in HDFn. By contrast, a hsa-miR-6727-5p inhibitor promoted wound closure in HDFa. We conclude that HDL treatment exerts distinct effects on the expression of hsa-miR-6727-5p in neonatal and adult fibroblasts, and that this is a sequence which plays differential roles in wound healing in these cell types, but cannot replicate the myriad ef-fects of HDL.
Original languageEnglish
Article number154
Number of pages19
JournalMembranes
Volume12
Issue number2
DOIs
Publication statusPublished - 27 Jan 2022

Keywords

  • high-density lipoproteins; adult fibroblast; neonatal fibroblast; wound healing; microRNA
  • MicroRNA
  • Wound healing
  • High-density lipoproteins
  • Neonatal fibroblast
  • Adult fibroblast

ASJC Scopus subject areas

  • Chemical Engineering (miscellaneous)
  • Process Chemistry and Technology
  • Filtration and Separation

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