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

Abstract

The objective of this work was to examine myomiR levels in plasma, skeletal muscle, and skeletal muscle cells of patients with idiopathic inflammatory myopathy (IIM), and their interrelations with the disease-related clinical phenotypes and with the effects of a disease-modifying 6-months-training intervention. Samples of vastus lateralis muscle (n = 12/13) and plasma (n = 21/20) were obtained from IIM patients and healthy controls, respectively. The muscle and plasma samples were obtained before and after a 6-months training intervention in 7 patients. MyomiRs miR-1, -206, -133a, and -133b were quantified using quantitative PCR (qPCR). The effects of pro-inflammatory (TNF) and metabolic (glucose, insulin) systemic factors and of immunosuppressive therapy (dexamethasone) on the myomiRs were examined in muscle cells in vitro. MiR-133b was lower in the skeletal muscle of IIM patients than in that of healthy controls (P = 0.03). The levels of miR-133a, miR-1, and miR-206 were not regulated. Moreover, the plasma levels of miR-133b and miR-1 were reduced in patients with IIM compared with those in healthy controls (P <0.05). It was observed that exercise induced reciprocal regulation of specific myomiRs in the muscle and plasma of patients with IIM: it lowered miR-133b in muscle while increasing miR-133b and miR-206 in plasma. Treatment of myotubes with TNF, insulin, glucose and dexamethasone (individually) induced the downregulation of distinct myomiRs. Lower myomiR levels in the 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 in muscle and plasma myomiRs indicate an increase in the release of myomiRs, which could contribute to the adaptive response underlying the positive systemic effects of exercise in IIM. ISRCTN register, https://www.isrctn.com/ ISRCTN35925199.