title: Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy.
abstract: OBJECTIVE
  The 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 fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD).
  
  
  METHODS
  Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay.
  
  
  RESULTS
  Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The 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.
  
  
  CONCLUSIONS
  Our findings 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 fibrosis.
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.|Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Fuchen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.
authors.forename: Zonglai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jian, China.|Key Laboratory for Experimental Teratology of the Ministry of Education, School of Medicine, Shandong University, Jian, China.|Brain Science Research Institute, Shandong University, Jian, China. chuanzhuyan@163.com.
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Yan
keywords: dermatomyositis; duchenne muscular dystrophy; muscle biopsy; polymyositis; β-catenin