Muscle-specific miRNAs in plasma and skeletal muscle of patients with idiopathic inflammatory myopathy are modulated by disease and training.

Objectives: Objective of this work was to examine myomiR levels in plasma, skeletal muscle, and skeletal muscle cells of patients with idiopathic inflammatory myopathy (IIM), their interrelations with the disease-related clinical phenotypes and with the effects of the disease-modifying 6-month training-intervention.

Methods: Samples of vastus lateralis muscle (n = 12/13) and plasma (n = 20/21) were obtained from IIM patients and healthy controls, respectively. Muscle and plasma were obtained before and after a 6-month training-intervention in 7 patients. MyomiRs miR-1,-206,-133a,-133b were quantified by qPCR. Effects of pro-inflammatory (TNF), metabolic (glucose, insulin) systemic factors and the immunosuppressive therapy (dexamethasone) on the myomiRs were examined in muscle cells in vitro.

Results: MiR-133b was lower in skeletal muscle of IIM patients compared with healthy controls (p= 0.03). Levels of miR-133a, miR-1, and miR-206 were not regulated. Moreover, plasma levels of miR-133b and miR-1 were reduced in IIM compared with healthy controls (p< 0.05). Exercise induced reciprocal regulation of specific myomiRs in muscle and plasma of IIM patients, it lowered miR-133b in muscle while increasing miR-133b and miR-206 in plasma. Treatment of myotubes with TNF, insulin, and glucose and dexamethasone induced distinct myomiRs down-regulation.

Conclusion: Lower myomiR levels in skeletal muscle of IIM patients might indicate reduced muscle regenerative potential in IIM, which could be linked to inflammation, metabolic dysfunction, and immunosuppressive therapy. Training-induced changes of muscle and plasma myomiRs indicate an increase in myomiRs release, which could contribute to the adaptive response underlying the positive systemic effects of exercise in IIM.