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        Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy

        Fuchen Liu,Zonglai Liang,Jingwen Xu,Wei Liu,Dandan Zhao,Yuying Zhao,Chuanzhu Yan 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.3

        Background and PurposezzTe wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fbrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). MethodszzImmunofuorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. Te β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shif assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. ResultszzImmunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fbers in PM, DM, and DMD. Te protein level of β-catenin was elevated, and EMSA analysis confrmed the activation of wnt/β-catenin signaling. Te transcriptional activities of β-catenin/ Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. ConclusionszzOur fndings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fbrosis.

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