MiR-10a and miR-181c regulate collagen type I generation in hypertrophic scars by targeting PAI-1 and uPA

FEBS Lett. 2015 Jan 30;589(3):380-9. doi: 10.1016/j.febslet.2014.12.024. Epub 2014 Dec 29.

Abstract

Urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been proposed to play key roles in extracellular matrix (ECM) deposition in hypertrophic scars (HS). Here, we found that in HS fibroblasts (HFs) miR-181c and miR-10a were differentially-expressed and targeted uPA and PAI-1, respectively. The production of Type 1 collagen (Col1) was inhibited by miR-181c knockdown or miR-10a overexpression in HFs, and this resulted in increased levels of metalloproteinase 1 (MMP1). These results suggest that the miR-181c-uPA and miR-10a-PAI-1 regulatory pathways have an integral role in HS pathogenesis.

Keywords: Collagen type 1; Hypertrophic scar; MicroRNA; Plasminogen activator inhibitor-1; Urokinase type plasminogen activator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cicatrix, Hypertrophic / genetics*
  • Cicatrix, Hypertrophic / pathology
  • Collagen Type I / biosynthesis*
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 1 / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Urokinase-Type Plasminogen Activator / genetics*
  • Urokinase-Type Plasminogen Activator / metabolism
  • Young Adult

Substances

  • Collagen Type I
  • MIRN10 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • Plasminogen Activator Inhibitor 1
  • Urokinase-Type Plasminogen Activator
  • MMP1 protein, human
  • Matrix Metalloproteinase 1