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

BACKGROUND AND PURPOSE: 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.

Characteristics of facioscapulohumeral muscular dystrophy's vascular inflammatory pathological changes / 中华神经科杂志

Objective To investigate the pathological features of blood vessel inflammation in facioscapulohumeral muscular dystrophy ( FSHD ) and the role of vasculitis on the pathogenesis of FSHD. Methods The clinical manifestations and myopathological features of 26 FSHD patients were retrospectively analyzed and summarized. All of the patients were divided into 2 groups; inflammatory infiltration group and non-inflammatory infiltration group. The latter was further divided into 3 subgroups;endomysial inflammation subgroup, perivasculitis subgroup and transmural vasculitis subgroup.Immunohistochemical staining were carried out in inflammatory infiltration group with anti-CD3, anti-CD4,anti-CD8,anti-CD20 and anti-SMA antibody. The control group was composed of 10 dermatomyositis ( DM)cases and 10 polymyositis ( PM) cases. Results The age of onset was (25. 2 ± 12. 6) years old and the average course was (7. 8 ±7. 3) years. The sex ratio of male to female was 1.6: 1. Five of them had family history. The main clinical features were progressive weakness and atrophy of facial, shoulder girdles and proximal upper limbs muscles. The lower distal limbs and (or) lower distal limbs and pelvic girdle muscles were involved in 18 cases. The main pathological features were shown as followed. Seventeen of them had focal inflammatory cell infiltration, including endomysial inflammation (4/17) , perivasculitis (7/17) , and transmural vasculitis (6/17). Immunohistochemical staining confirmed the major types of inflammatory cells were CD4* T lymphocytes and CD20B lymphocytes, which was familiar with DM. While in PM, CD8+ T lymphocytes were dominant The proportionality of residual muscle fibers obviously decreased in inflammatory infiltration group ( 48. 0% ± 23. 6% ) than non-inflammatory infiltration group ( 94. 3% ±3. 1% , T = 198. 000, P = 0. 000). As to CK levels, there were no significant deviation. Conclusions Obvious inflammatory cell infiltration can be seen in FSHD, the locations of inflammatory cells are endomyosium inflammation, perivasculitis and transmural vasculitis. Transmural vasculitis indicates vascular pathological factor may have something to do with pathogenesis of FSHD.

The pathological characteristics of plasmacytoid dendritic cells in muscle tissue of dermatomyositis / 中华神经科杂志

Objective To study the histological features of plasmacytoid dendritic cells (pDC) in muscle tissue affected by dermatomyositis (DM) and to discuss the pathological significations of pDC.Methods Muscle tissues from 30 cases of DM and 25 cases of polymyositis (PM) were collected.HE stain, immunohistochemistry studies were carried out in all muscle samples.Results Pathological features of DM included: perifascicular atrophy (25/30); punched-out fiber (14/30); perivasculitis (17/30),inflammatory infiltration in the endomysium(6/30).Using immunohistochemistry study, 19 cases from DM were infiltrated by macrophages which are CD68 positive and CD303 negative, 20 cases with DM were infiltrated by pDC which are CD303 positive.The location of pDC were: perivascular of interfascicular septae only (15/20); endomysium only (3/20) and both (2/20).Myopathic damage such as necrotic and regenerating fibers and inflammatory infiltration could be seen in PM.There was few pDC infiltration in PM.Conclusions There is few pDC in muscle tissue affected by PM and many pDC in muscle tissue affected by DM with infiltration mainly in the wide interfascicular septae.pDC may be connected to perifascicular atrophy and play a roll in the pathogenesis of DM.