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• W2100648028 endingPage "1505" @default.
• W2100648028 startingPage "1492" @default.
• W2100648028 abstract "Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by loss of functional dystrophin protein. Accumulating evidence suggests that the deficiency of dystrophin leads to aberrant activation of many signaling pathways which contribute to disease progression. However, the proximal signaling events leading to the activation of various pathological cascades in dystrophic muscle remain less clear. TNF receptor-associated factor 6 (TRAF6) is an adaptor protein which acts as a signaling intermediate for several receptor-mediated signaling events leading to the context-dependent activation of a number of signaling pathways. TRAF6 is also an E3 ubiquitin ligase and an important regulator of autophagy. However, the role of TRAF6 in pathogenesis of DMD remains unknown. Here, we demonstrate that the levels and activity of TRAF6 are increased in skeletal muscle of mdx (a mouse model of DMD) mice. Targeted deletion of TRAF6 improves muscle strength and reduces fiber necrosis, infiltration of macrophages and the activation of proinflammatory transcription factor nuclear factor-kappa B (NF-κB) in 7-week-old mdx mice. Ablation of TRAF6 also increases satellite cells proliferation and myofiber regeneration in young mdx mice. Intriguingly, ablation of TRAF6 exacerbates muscle injury and increases fibrosis in 9-month-old mdx mice. TRAF6 inhibition reduces the markers of autophagy and Akt signaling in dystrophic muscle of mdx mice. Collectively, our study suggests that while the inhibition of TRAF6 improves muscle structure and function in young mdx mice, its continued inhibition causes more severe myopathy at later stages of disease progression potentially through repressing autophagy." @default.
• W2100648028 created "2016-06-24" @default.
• W2100648028 creator A5000895178 @default.
• W2100648028 creator A5047468489 @default.
• W2100648028 creator A5074350735 @default.
• W2100648028 creator A5079411311 @default.
• W2100648028 date "2013-10-24" @default.
• W2100648028 modified "2023-09-26" @default.
• W2100648028 title "Distinct roles of TRAF6 at early and late stages of muscle pathology in the mdx model of Duchenne muscular dystrophy" @default.
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• W2100648028 doi "https://doi.org/10.1093/hmg/ddt536" @default.
• W2100648028 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3929088" @default.
• W2100648028 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24163132" @default.
• W2100648028 hasPublicationYear "2013" @default.
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