Effects of Exercise on microRNA Expression in Young Males Peripheral Blood Mononuclear Cells

Abstract

MicroRNAs are increasingly seen as targets of drug discovery because they influence gene function acting both to silence and subtly modulate protein translation. Little is known about effects of dynamic physiological states on microRNA regulation in humans. We hypothesized that microRNA expression in peripheral blood mononuclear cells (PBMCs) would be affected by brief exercise. Twelve young men performed brief bouts of heavy exercise. PBMC microRNA was analyzed before and immediately after exercise using the Agilent Human microRNA V2 Microarray. Exercise altered expression level of 34 microRNAs (FDR < 0.05). Many of them play roles in inflammatory processes (e.g., miR-125b[↓], down-regulated by proinflammatory factor LPS; and miR-132[↑], 125b[↓] and let-7e[↓] involved inTLR4 signaling). Using previous exercise data in PBMCs, we linked the microRNA changes to specific gene pathways. This analysis identified 12 pathways including the TGF-β and MAPK signaling. We also compared exercise-associated microRNA changes in PBMCs with the exercise-associated microRNAs previously identified in neutrophils. Nine microRNAs were affected in both PBMCs and neutrophils, but only six changed in the same direction. A commonly occurring physiologic perturbation, brief heavy exercise, changes microRNA profiles in PBMCs, many of which are related to inflammatory processes. The pattern of change suggests that exercise differentially influences microRNAs in leukocyte subtypes.

Circulating inflammatory miRNA signature in response to different doses of aerobic exercise

“…However, previous data about the mechanisms in which our altered c-inflammamiRs participate, together with correlation analysis, support a role for these mediators in the exercise-induced inflammatory response. Intracellular expression of the let-7 family members miR-125b, -132, -143, -150, -223, -29a, and -34a is a highly regulated process induced by inflammatory stimuli and signals (35,48,49,79), including acute exercise (59,60). c-InflammamiRs for which significant alterations were observed are implicated in the tight regulation of the inflammatory response at different levels.…”

Regulation of Gene Expression by Exercise-Related Micrornas

“…These changes were associated with altered cell function and increased risk of atherosclerosis [130,131]. Radom-Aizik et al [132] studied miR expression modulation in peripheral blood mononuclear cells (PBMC) by brief exercise. In this study, twelve young men performed brief bouts of heavy exercise consisted by 20 minutes of exercise involving ten 2-minute bouts of constant work rate cycle ergometry, with 1-minute rest interval between each bout of exercise.…”

“…The miRs 181a and 181b were upregulated by brief exercised and may be involved with the monocyte function modulated by physical exercise in patients with asthma [132]. Expression of miR-181 family (miR-181a and miR-181b) is modulated in different types of leukocytes in response to physical exercise [132,134].…”

“…Expression of miR-181 family (miR-181a and miR-181b) is modulated in different types of leukocytes in response to physical exercise [132,134]. MiR-181 suppresses inflammatory response induced by oxidated low-density lipoprotein in dendritic cells [135] and miR 181b inhibits inflammatory response mediated by nuclear factor-kappa B transcription factor [136].…”

“…Radom-Aizik et al [132] described that in comparison to neutrophils changes, nine microRNAs were modulated in PBMCs, but only six changed in the same course. These observations suggest that exercise differentially modulate miRs in several leukocyte subtypes.…”