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

Millar, N. L. , Gilchrist, D., Akbar, M., Reilly, J. H., Kerr, S. C., Campbell, A. L., Murrell, G. A.C., Liew, F. Y., Kurowska-Stolarska, M. and McInnes, I. B. (2015) MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease. Nature Communications, 6, 6774. (doi: 10.1038/ncomms7774) (PMID:25857925) (PMCID:PMC4403384)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Prof Foo and Kurowska-Stolarska, Professor Mariola and Akbar, Mr Moeed and Reilly, Mr James and Kerr, Mrs Shauna and Gilchrist, Dr Derek and Millar, Professor Neal
Authors: Millar, N. L., Gilchrist, D., Akbar, M., Reilly, J. H., Kerr, S. C., Campbell, A. L., Murrell, G. A.C., Liew, F. Y., Kurowska-Stolarska, M., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 Macmillan Publishers
First Published:First published in Nature Communications 6:6774
Publisher Policy:Reproduced under a Creative Commons License
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WT100651