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MyomiRs in cultured muscle cells from patients with idiopathic inflammatory myopathy are modulated by disease but not by 6-month exercise training

N. Alchus Laiferová, M. Nemec, L. Vernerová, M. Balážová, M. Vokurková, S. Oreská, M. Klein, M. Špiritović, M. Tomčík, J. Vencovský, J. Ukropec, B. Ukropcová

. 2022 ; 40 (2) : 346-357. [pub] 20220225

Jazyk angličtina Země Itálie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22011111

OBJECTIVES: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls. METHODS: Samples of m. vastus lateralis were obtained by needle biopsy from IIM patients before/after 6-month training and from matched sedentary healthy controls. Muscle cell cultures were established and exposed to saturated fatty acid during differentiation. MiR-133a,-133b,-206,-1 and their target genes (qPCR), fat oxidation (FOx), lipids (chromatography) and mitochondrial oxidative phosphorylation (OxPHOS) complexes (immunoblotting) were measured. Interrelations between in vitro miRs and metabolism of myotubes as well as clinical parameters and disease activity/MITAX were explored. RESULTS: Levels of miRs were higher in myotubes derived from IIM patients compared to healthy controls (up to 3.5-fold, p<0.05). Neither 6-month training (IIM patients) nor in vitro palmitate treatment modulated myomiRs in myotubes. However, miR-133a,-133b, and miR-1 correlated negatively with FOx (p<0.01), triacylglycerols (p<0.05) and OxPHOS complex-V (p<0.05) and positively with OxPHOS complex-I (p<0.05) in myotubes. MiR-133a and miR-133b in myotubes were related to disease activity and fasting glycaemia in vivo (both p<0.05). CONCLUSIONS: Upregulation of microRNAs involved in myogenesis and regeneration in muscle cells derived from IIM patients indicates activation of compensatory epigenetic mechanisms, potentially aimed to counteract disease progression. Relationships of microRNAs with in vitro metabolic profile of muscle cells as well as with clinical parameters support the role of muscle-specific microRNAs in modulating muscle metabolism and clinical state of patients.

Citace poskytuje Crossref.org

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$a OBJECTIVES: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls. METHODS: Samples of m. vastus lateralis were obtained by needle biopsy from IIM patients before/after 6-month training and from matched sedentary healthy controls. Muscle cell cultures were established and exposed to saturated fatty acid during differentiation. MiR-133a,-133b,-206,-1 and their target genes (qPCR), fat oxidation (FOx), lipids (chromatography) and mitochondrial oxidative phosphorylation (OxPHOS) complexes (immunoblotting) were measured. Interrelations between in vitro miRs and metabolism of myotubes as well as clinical parameters and disease activity/MITAX were explored. RESULTS: Levels of miRs were higher in myotubes derived from IIM patients compared to healthy controls (up to 3.5-fold, p<0.05). Neither 6-month training (IIM patients) nor in vitro palmitate treatment modulated myomiRs in myotubes. However, miR-133a,-133b, and miR-1 correlated negatively with FOx (p<0.01), triacylglycerols (p<0.05) and OxPHOS complex-V (p<0.05) and positively with OxPHOS complex-I (p<0.05) in myotubes. MiR-133a and miR-133b in myotubes were related to disease activity and fasting glycaemia in vivo (both p<0.05). CONCLUSIONS: Upregulation of microRNAs involved in myogenesis and regeneration in muscle cells derived from IIM patients indicates activation of compensatory epigenetic mechanisms, potentially aimed to counteract disease progression. Relationships of microRNAs with in vitro metabolic profile of muscle cells as well as with clinical parameters support the role of muscle-specific microRNAs in modulating muscle metabolism and clinical state of patients.
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$a Nemec, Michal $u Institute of Experimental Endocrinology, Biomedical Research Centre, Slovak Academy of Sciences, Bratislava, Slovakia
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$a Vernerová, Lucia $u Institute of Rheumatology, Prague, Czech Republic
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$a Balážová, Mária $u Centre of Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia
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$a Vokurková, Martina $u Institute of Rheumatology, Prague, Czech Republic
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$a Oreská, Sabína $u Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Klein, Martin $u Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Špiritović, Maja $u Institute of Rheumatology, Prague, and Department of Physiotherapy, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic
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$a Tomčík, Michal $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Vencovský, Jiří $u Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Ukropec, Jozef $u Institute of Experimental Endocrinology, Biomedical Research Centre, Slovak Academy of Sciences, Bratislava, Slovakia
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