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MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease.
- Source :
-
Nature communications [Nat Commun] 2015 Apr 10; Vol. 6, pp. 6774. Date of Electronic Publication: 2015 Apr 10. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Collagen Type I genetics
Collagen Type I metabolism
Collagen Type III genetics
Collagen Type III metabolism
Fibroblasts drug effects
Fibroblasts pathology
Gene Expression Regulation
Genes, Reporter
Humans
Interleukin-1 Receptor-Like 1 Protein
Interleukin-1beta pharmacology
Interleukin-33 metabolism
Luciferases genetics
Luciferases metabolism
Mice
MicroRNAs antagonists & inhibitors
MicroRNAs metabolism
Primary Cell Culture
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Receptors, Cell Surface genetics
Receptors, Cell Surface metabolism
Signal Transduction
Tendinopathy metabolism
Tendinopathy pathology
Tendons drug effects
Tendons pathology
Tumor Necrosis Factor-alpha pharmacology
Fibroblasts metabolism
Interleukin-33 genetics
MicroRNAs genetics
Tendinopathy genetics
Tendons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25857925
- Full Text :
- https://doi.org/10.1038/ncomms7774