MicroRNAs in skeletal muscle biology and exercise adaptation

Abstract

MicroRNAs (miRNAs) have emerged as important players in the regulation of gene expression, being involved in most biological processes examined to date. The proposal that miRNAs are primarily involved in the stress response of the cell makes miRNAs ideally suited to mediate the response of skeletal muscle to changes in contractile activity. Although the field is still in its infancy, the studies presented in this review highlight the promise that miRNAs will have an important role in mediating the response and adaptation of skeletal muscle to various modes of exercise. The roles of miRNAs in satellite cell biology, muscle regeneration, and various myopathies are also discussed.

Keywords: Exercise; Free radicals; MicroRNA; MyomiR; Skeletal muscle.

Figure 1. MicroRNA regulation of resistance exercise adaptations

Acute resistance exercise decreases miR-1 in skeletal muscle, leading to increased IGF1/AKT signaling and therefore, increased protein synthesis. In response to chronic resistance exercise, low-responders showed a decrease in miR-378 expression, a miRNA shown to regulate mitochondrial biogenesis via upregulation of PGC-1β expression. Conversely, the high responders maintained their levels of miR-378, which is proposed to regulate myogenic differentiation by increased MyoD expression via repression of MyoR expression. Red arrow indicates downregulation of miRNA or gene expression. Solid line indicates validated gene target of miRNA, while dashed line indicates predicted gene target of miRNA.

Figure 2. MicroRNA regulation of endurance exercise adaptations

Endurance exercise results in the downregulation of miR-23 and miR-494 expression in skeletal muscle which is predicted to promote mitochondrial biogenesis via upregulation of PGC-1α, mtTFA and Foxj3. In Addition, miR-19 is downregulated which is predicted in increase angiogenesis by upregulation of Vegf and Vegfr. Endurance exercise decreases circulating levels of miR-486 which could promote a negative protein balance via regulation of Pten and Foxo. Finally, miR-29 levels are increased in the left ventricle following endurance exercise which is proposed to increase ventricular compliance by repressing multiple collagens. Green arrow indicates upregulation of miRNA or gene expression. Red arrow indicates downregulation of miRNA or gene expression. Solid line indicates validated gene target of miRNA, while dashed line indicates predicted gene target of microRNA.

Figure 3. MicroRNAs and target genes involved in muscle regeneration

In response to cardiotoxin injury, activated satellite cells begin to proliferate and then proceed through myogenic differentiation as part of the regenerative process. Satellite cell proliferation and differentiation are associated with changes in miRNA expression that result in an alteration in target gene expression that have been shown to be important for proper muscle regeneration. Green arrow indicates upregulation of miRNA or gene expression. Red arrow indicates downregulation of miRNA or gene expression.