title: Peroxisome Proliferator Activated Receptor Beta (PPARβ) activity increases the immune response and shortens the early phases of skeletal muscle regeneration.
abstract: Peroxisome Proliferator-Activated Receptor Beta (PPARβ) is a transcription factor playing an important role in both muscle myogenesis and remodeling, and in inflammation. However, its role in the coordination of the transient muscle inflammation and reparation process following muscle injury has not yet been fully determined. We postulated that activation of the PPARβ pathway alters the early phase of the muscle regeneration process, i.e. when immune cells infiltrate in injured muscle. Tibialis anteriors of C57BL6/J mice treated or not with the PPARβ agonist GW0742 were injected with cardiotoxin (or with physiological serum for the contralateral muscle). Muscle regeneration was monitored on days 4, 7, and 14 post-injury. We found that treatment of mice with GW0742 increased, at day 4 post-damage, the recruitment of immune cells (M1 and M2 macrophages) and upregulated the expression of the anti-inflammatory cytokine IL-10 and TGF-β mRNA. Those effects were accompanied by a significant increase at day 4 of myogenic regulatory factors (Pax7, MyoD, Myf5, Myogenin) mRNA in GW0742-treated mice. However, we showed an earlier return (7 days vs 14 days) of Myf5 and Myogenin to basal levels in GW0742- compared to DMSO-treated mice. Differential effects of GW0742 observed during the regeneration were associated with variations of PPARβ pathway activity. Collectively, our findings indicate that PPARβ pathway activity shortens the early phases of skeletal muscle regeneration by increasing the immune response.
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mothe-Satney
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Piquet
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Murdaca
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sibille
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Grimaldi
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France.
authors.forename: Jaap G
authors.initials: JG
authors.lastname: Neels
authors.affiliation: Université Côte d'Azur, Inserm, C3M, Nice, France. Electronic address: Anne-Sophie.ROUSSEAU@unice.fr.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Rousseau
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D048068:PPAR-beta / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology; D014158:Transcription, Genetic; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D048068:PPAR-beta; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds
keywords: Inflammation; Macrophage; Muscle injury; Peroxisome proliferator activated receptor; Reparation