RESUMEN
BACKGROUND: Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN. METHODS: Primary cultures of myotubes from DMD and control patients were treated or not by ApN after an inflammatory challenge. Myokines secreted in medium were identified by cytokine antibody-arrays and ELISAs. The early events of ApN signaling were assessed by abrogating selected genes. RESULTS: ApN retained its anti-inflammatory properties in both dystrophic and control myotubes. Profiling of secretory products revealed that ApN downregulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) in DMD myotubes, while upregulating IL-6 that exerts some anti-inflammatory effects. These changes were explained by pretranslational mechanisms. Earlier events of the ApN cascade involved AdipoR1, the main receptor for muscle, and the AMPK-SIRT1-PGC-1α axis leading, besides alteration of the myokine profile, to the upregulation of utrophin A (a dystrophin analog). CONCLUSION: ApN retains its beneficial properties in dystrophic muscles by activating the AdipoR1-AMPK-SIRT1-PGC-1α pathway, thereby inducing a shift in the secretion of downstream myokines toward a less inflammatory profile while upregulating utrophin. ApN, the early events of the cascade and downstream myokines may be therapeutic targets for the management of DMD.
Asunto(s)
Adiponectina/metabolismo , Antiinflamatorios/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Proteoma/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Niño , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/metabolismo , Inflamación/patología , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Receptores de Adiponectina/metabolismo , Sirtuina 1/metabolismo , Utrofina/genética , Utrofina/metabolismo , Adulto JovenAsunto(s)
Fibrosis Quística/fisiopatología , Fibrosis Quística/psicología , Indicadores de Salud , Calidad de Vida , Encuestas y Cuestionarios/normas , Actividades Cotidianas , Adolescente , Factores de Edad , Niño , Fibrosis Quística/clasificación , Fibrosis Quística/diagnóstico , Estudios de Evaluación como Asunto , Femenino , Flujo Espiratorio Forzado , Volumen Espiratorio Forzado , Humanos , Masculino , Análisis de Regresión , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Estados Unidos , Población Urbana , Capacidad VitalRESUMEN
This study assesses the role of child gender in moderating the association between husbands' aggression toward wives and parental aggression toward children. Participants were 73 mothers who experienced at least one incident of marital aggression during the past 12 months. Each mother had a child between 5 and 16 years of age. Hierarchical regression analyses indicate that the Husbands' Aggression Toward Wives x Child Gender interaction contributed unique variance to the prediction of both mothers' and fathers' aggression toward children after husbands' aggression toward wives, child gender, and child age were controlled. Pearson correlations indicate that husbands' aggression toward wives correlated positively with mothers' and fathers' aggression toward boys but not toward girls.
