title: New targets to alleviate skeletal muscle inflammation: role of microRNAs regulated by adiponectin.
abstract: Muscle inflammation worsens metabolic disorders as well as devastating myopathies. The hormone adiponectin (ApN) has emerged has a master regulator of inflammation/immunity in several tissues including the skeletal muscle. In this work, we explore whether microRNAs regulated by ApN may represent novel mechanisms for controlling muscle inflammation. By screening arrays, we found miR-711 as a strong candidate for mediating ApN action. Thus, ApN-knockout mice showed decreased muscular expression of miR-711 together with enhanced inflammation/oxidative stress markers, while mice overexpressing ApN showed increased miR-711 levels. Likewise, electrotransfer of the ApN gene in muscle of ApN-knockout mice upregulated miR-711 while reducing inflammation and oxidative stress. Similar data were obtained in murine C2C12 cells or in human primary myotubes treated with ApN. MiR-711 overexpression downregulated several components of the Toll-like receptor-4 (TLR4) pathway, which led to repression of NF-κB activity and downstream pro-inflammatory cytokines. MiR-711 blockade had opposite effects. Moreover, muscle electrotransfer of pre-miR-711 recapitulated in vivo the anti-inflammatory effects observed in vitro. Thus, miR-711, which is upregulated by ApN represses TLR4 signaling, acting therefore as a major mediator of the anti-inflammatory action of ApN. This novel miRNA and its related target genes may open new therapeutic perspectives for controlling muscle inflammation.
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research and Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Boursereau
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research and Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Abou-Samra
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research and Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lecompte
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research and Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Noel
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research and Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Brichard
mesh_terms: D052242:Adiponectin / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D053672:Electrochemotherapy / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D035683:MicroRNAs; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4