title: MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease.
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.
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Neal L
authors: NL
authors: Millar
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Derek S
authors: DS
authors: Gilchrist
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Moeed
authors: M
authors: Akbar
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: James H
authors: JH
authors: Reilly
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Shauna C
authors: SC
authors: Kerr
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Abigail L
authors: AL
authors: Campbell
authors: Orthopaedic Research Institute, Department of Orthopaedic Surgery, St George Hospital Campus, University of New South Wales, Sydney, New South Wales NSW 2217, Australia.
authors: George A C
authors: GAC
authors: Murrell
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.|School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215006, China.
authors: Foo Y
authors: FY
authors: Liew
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Mariola
authors: M
authors: Kurowska-Stolarska
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, Glasgow G12 8QQ, UK.
authors: Iain B
authors: IB
authors: McInnes
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta / Q000494:pharmacology; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D052256:Tendinopathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013710:Tendons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases