Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis
| Autor: | Alicia Alonso-Jimenez, Eduard Gallardo, Ana Milena-Millan, Hèctor Corominas, Ana Carrasco-Rozas, Laura Martínez-Martínez, Ricardo Rojas-García, Carlos Zamora, Xavier Suárez-Calvet, Diego Castillo, Isabel Illa, Ivan Castellví, Elena Cortés-Vicente, Luis Querol, Jorge Alonso-Pérez, Noemi de Luna, Jordi Díaz-Manera, Joana Turón, Esther Fernández-Simón |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Inflammation Article Thrombospondin 1 Inflammatory myopathy Neck Muscles Humans Medicine Myocyte Muscle Skeletal Myopathy skin and connective tissue diseases Aged Muscle Weakness Scleroderma Systemic Muscle biopsy Myositis medicine.diagnostic_test integumentary system business.industry Myogenesis Muscle weakness Middle Aged medicine.disease Hypotonia Neurology Arm Female Neurology (clinical) medicine.symptom business |
| Zdroj: | Neurology-Neuroimmunology & Neuroinflammation r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname Neurology® Neuroimmunology & Neuroinflammation |
| ISSN: | 2332-7812 |
| Popis: | ObjectiveTo describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients.MethodsWe reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo.ResultsAll patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle.ConclusionsPatients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|