| Autor: |
Vernerová, Lucia, Horváthová, Veronika, Kropáčková, Tereza, Vokurková, Martina, Klein, Martin, Tomčík, Michal, Oreská, Sabína, Špiritović, Maja, Štorkánová, Hana, Heřmánková, Barbora, Kubínová, Kateřina, Kryštůfková, Olga, Mann, Heřman, Ukropec, Jozef, Ukropcová, Barbara, Vencovský, Jiří |
| Předmět: |
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| Zdroj: |
Rheumatology; Sep2020, Vol. 59 Issue 9, p2491-2501, 11p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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