MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

Nat Commun. 2015 Apr 10;6:6774. doi: 10.1038/ncomms7774.

Abstract

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-1beta / pharmacology
  • Interleukin-33 / genetics*
  • Interleukin-33 / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Primary Cell Culture
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Tendinopathy / genetics*
  • Tendinopathy / metabolism
  • Tendinopathy / pathology
  • Tendons / drug effects
  • Tendons / metabolism*
  • Tendons / pathology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Collagen Type I
  • Collagen Type III
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-1beta
  • Interleukin-33
  • MIRN29 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Luciferases