Effect of endurance exercise on microRNAs in myositis skeletal muscle—A randomized controlled study

Abstract

ObjectiveTo identify changes in skeletal muscle microRNA expression after endurance exercise and associate the identified microRNAs with mRNA and protein expression to disease-specific pathways in polymyositis (PM) and dermatomyositis (DM) patients.MethodsFollowing a parallel clinical trial design, patients with probable PM or DM, exercising less than once a week, and on stable medication for at least one month were randomized into two groups at Karolinska University Hospital: a 12-week endurance exercise group (n = 12) or a non-exercised control group (n = 11). Using an Affymetrix microarray, microRNA expression was determined in paired muscle biopsies taken before and after the exercise intervention from 3 patients in each group. Ingenuity pathway analysis with a microRNA target filter was used to identify microRNA transcript targets. These targets were investigated at the mRNA (microarray) and protein (mass spectrometry) levels in patients.ResultsEndurance exercise altered 39 microRNAs. The microRNAs with increased expression were predicted to target transcripts involved in inflammatory processes, metabolism, and muscle atrophy. Further, these target transcripts had an associated decrease in mRNA expression in exercised patients. In particular, a decrease in the NF-κB regulator IKBKB was associated with an increase in its target microRNA (miR-196b). At the protein level, there was an increase in mitochondrial proteins (AK3, HIBADH), which were associated with a decrease in microRNAs that were predicted to regulate their expression.ConclusionImprovement in disease phenotype after exercise is associated with increasing microRNAs that target and downregulate immune processes at the transcript level, as well as decreasing microRNAs that target and upregulate mitochondrial content at the protein level. Therefore, microRNAs may improve disease by decreasing immune responses and increasing mitochondrial biogenesis.Trial registrationClinicalTrials.gov NCT01184625

Master athletes have higher miR-7, SIRT3 and SOD2 expression in skeletal muscle than age-matched sedentary controls

“…For instance, both short- [19] and long-term endurance exercise [20] induced changes in the levels of a number of miRNAs that are involved in the regulation of skeletal muscle regeneration, gene expression and mitochondrial biogenesis. These effects of endurance training are not limited to healthy people, but also in patients with polymyositis or dermatomyositis endurance exercise induced an increase in muscle miRNA levels that target transcripts involved in inflammation, metabolism and muscle atrophy [21] . Hypertrophic stimuli can also induce changes in miRNA levels as illustrated by our observation that functional mechanical overloading by synergist muscle ablation induced alterations in miRNA levels that control atrophy and hypertrophy [22] .…”

Exercise in Myositis

“…No similar response was identified in the non-exercising control group [ 34 ••]. Analysis of a smaller sub-set of patients from the RCT by Alemo Munters et al (2013) [ 32 ] revealed changes in microRNAs targeting transcripts and proteins that are important for immune and muscle response [ 41 ••]. These studies further support the hypothesis that exercise is a disease-modifying treatment and an important part of the treatment in patients with PM and DM.…”

The Effect of MicroRNA-Mediated Exercise on Delaying Sarcopenia in Elderly Individuals

“…50,51 It was reported that endurance exercise changes the expression levels of 39 miRNAs. 52 It is predicted that the miRNAs exhibiting increased expression target transcripts involved in inflammatory processes, metabolism and muscle atrophy, and miRNAs affect muscle atrophy through the reduction of mitochondrial biogenesis. 52 IGF-1 is known to be an effective promoter of muscle growth.…”

“… 52 It is predicted that the miRNAs exhibiting increased expression target transcripts involved in inflammatory processes, metabolism and muscle atrophy, and miRNAs affect muscle atrophy through the reduction of mitochondrial biogenesis. 52 IGF-1 is known to be an effective promoter of muscle growth. After 12 weeks of resistance exercise training (RET) or eccentric ergometer training (EET), regulation of miR-1 led to significant increases in muscle fiber cross-sectional area.…”