Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity
| Autor: | Rabi Tawil, Christopher R. S. Banerji, Peter S. Zammit, Don Henderson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
AcademicSubjects/SCI01140 Adult Male Pathology medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Duchenne muscular dystrophy Muscle Fibers Skeletal Biology Muscle Development Severity of Illness Index Myoblasts 03 medical and health sciences 0302 clinical medicine Myosin Biopsy Genetics medicine Myocyte Facioscapulohumeral muscular dystrophy Humans Myotonic Dystrophy Regeneration Myopathy Muscle Skeletal Molecular Biology Genetics (clinical) 030304 developmental biology Aged 0303 health sciences medicine.diagnostic_test Myosin Heavy Chains Myogenesis Skeletal muscle General Medicine Middle Aged medicine.disease Muscular Dystrophy Facioscapulohumeral Muscular Dystrophy Duchenne medicine.anatomical_structure Female General Article medicine.symptom Transcriptome 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle, prompting this study. For comparison, we also examined the similarly slowly progressing myotonic dystrophy type 2 (DM2). To first investigate regeneration at the transcriptomic level, we used the 200 human gene Hallmark Myogenesis list. This myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myoblast counterparts, so is higher in myogenic differentiation. The myogenesis biomarker was also elevated in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies compared to control biopsies, and on meta-analysis for each condition. In addition, the myogenesis biomarker was a robust binary discriminator of FSHD, DM2 and DMD from controls. We also analysed muscle regeneration at the protein level by immunolabelling muscle biopsies for developmental myosin heavy chain. Such immunolabelling revealed one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibialis anterior. The mean proportion of regenerating myofibres per quadriceps biopsy was 0.48%, significantly less than 1.72% in the tibialis anterior. All DM2 muscle biopsies contained regenerating myofibres, with a mean of 1.24% per biopsy. Muscle regeneration in FSHD was correlated with the pathological hallmarks of fibre size variation, central nucleation, fibrosis and necrosis/regeneration/inflammation. In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pathology. |
| Databáze: | OpenAIRE |
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