MiR-138/peroxisome proliferator-activated receptor β signaling regulates human hypertrophic scar fibroblast proliferation and movement in vitro

J Dermatol. 2015 May;42(5):485-95. doi: 10.1111/1346-8138.12792. Epub 2015 Mar 6.

Abstract

Excessive scars affect a patient's quality of life, both physically and psychologically, by causing pruritus, pain and contractures. Because there is a poor understanding of the complex mechanisms underlying the processes of hypertrophic scar formation, most therapeutic approaches remain clinically unsatisfactory. In this study, we found that miR-138 was downregulated and peroxisome proliferator-activated receptor (PPARβ) was inversely upregulated in hypertrophic scar tissues compared to in paired normal skin tissues. Using a dual-luciferase assay, we validated that miR138 directly targets PPARβ and regulates its expression at the transcriptional and translational levels. In gain-and-loss experiments, we found that miR-138/PPARβ signaling regulated human hypertrophic scar fibroblast proliferation and movement, and affected scarring-related protein expression, which suggests that miR-138/PPARβ signaling is important for hypertrophic scarring. Thus, our study provides evidence to help determine whether miR-138/PPARβ signaling may be a potential target for hypertrophic scarring management.

Keywords: cell movement; hypertrophic scar; miR-138; microRNA; peroxisome proliferator-activated receptors; proliferation.

MeSH terms

  • Adolescent
  • Adult
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cicatrix, Hypertrophic / genetics*
  • Cicatrix, Hypertrophic / metabolism*
  • Cicatrix, Hypertrophic / pathology
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PPAR-beta / genetics
  • PPAR-beta / metabolism*
  • Signal Transduction
  • Transcription, Genetic
  • Young Adult

Substances

  • MIRN138 microRNA, human
  • MicroRNAs
  • PPAR-beta