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Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies
L. Vernerová, V. Horváthová, T. Kropáčková, M. Vokurková, M. Klein, M. Tomčík, S. Oreská, M. Špiritović, H. Štorkánová, B. Heřmánková, K. Kubínová, O. Kryštůfková, H. Mann, J. Ukropec, B. Ukropcová, J. Vencovský
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NV16-33746A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
Medline Complete (EBSCOhost)
od 1999-01-01 do Před 1 rokem
- MeSH
- aktivinové receptory typu I genetika MeSH
- folistatin analýza MeSH
- fyzikální vyšetření metody MeSH
- korelace dat MeSH
- kosterní svaly * metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myostatin analýza MeSH
- myozitida * krev diagnóza etiologie patofyziologie MeSH
- posouzení stavu pacienta MeSH
- protein Smad3 genetika MeSH
- proteinligasy komplexu SCF genetika MeSH
- proteiny související s folistatinem genetika MeSH
- signální transdukce MeSH
- stanovení celkové genové exprese MeSH
- svalová atrofie * metabolismus patologie MeSH
- svalové proteiny genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis. METHODS: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR. RESULTS: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls. CONCLUSION: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases.
Department of Rheumatology 1st Faculty of Medicine
Division of Experimental Rheumatology Institute of Rheumatology Prague
Institute of Pathophysiology Faculty of Medicine Comenius University Bratislava Slovakia
Citace poskytuje Crossref.org
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