Lidocaine promotes fibroblast proliferation after thermal injury via up-regulating the expression of miR-663 and miR-486

Kaohsiung J Med Sci. 2020 Apr;36(4):274-280. doi: 10.1002/kjm2.12166. Epub 2019 Dec 9.

Abstract

Thermal burn is a complex injury that induces pronounced inflammatory reactions and destruction of the microvasculature. Lidocaine, which is broadly used for pain relief, has been reported have the capacity to modulate wound healing processes. Seventeen burn injury patients with no treatment and nine controls were included in this study. The expression of 15 candidate miRNAs in the dermis samples were detected by qRT-PCR. The target genes were predicted using online bioinformatics tools and confirmed by dual luciferase assay and immunoblotting. The function of miR-486 and miR-663 on skin fibroblasts keratinocytes were determined by MTT assay and flow cytometry. The level of miR-486 and miR-663 was increased after burn injury, meanwhile, the highest level of miR-486 and miR-663 was found after lidocaine treatment. We identified that BCL2L14 was a direct target of both miR-486 and miR-663. Meanwhile, overexpression of miR-486 or miR-663 inhibit apoptosis and promoted proliferation of human skin fibroblasts keratinocytes. These results indicated that lidocaine treatment promoted the skin healing after thermal injury through up-regulating miR-486 and miR-663 expression, and partially explained how lidocaine modulates wound healing processes. This may provide an evidence for the therapeutic effect of lidocaine during skin healing process. However, the underlying mechanisms need to be further unveiled.

Keywords: lidocaine; miRNA; thermal injury; wound healing.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Burns / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Gene Ontology
  • Humans
  • Lidocaine / pharmacology*
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Up-Regulation / genetics*

Substances

  • BCL2L14 protein, human
  • MIRN486 microRNA, human
  • MIRN663 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Lidocaine