Selenoprotein K protects skeletal muscle from damage and is required for satellite cells-mediated myogenic differentiation ^☆

Abstract

The regeneration of adult skeletal muscle after injury is primarily initiated by satellite cells (SCs), but the regulatory mechanisms of cells committed to myogenic differentiation remain poorly explored. Small molecular selenoprotein K (SelK) plays crucial roles in the modulation of endoplasmic reticulum (ER) stress and against oxidative stress. Here, we first showed that SelK expression is activated in myogenic cells during differentiation both in vivo and in vitro. Meanwhile, loss of SelK delayed skeletal muscle regeneration, inhibited the development of myoblasts into myotubes, and was accompanied by reduced expression of myogenic regulatory factors (MRFs). Moreover, ER stress, intracellular reactive oxygen species (ROS), autophagy and apoptosis under myogenesis induction were more severe in SelK-deficient mice and cells than in the corresponding control groups. Supplementation with specific inhibitors to alleviate excessive ER stress or oxidative stress partly rescued the differentiation potential and formation of myotubes. Notably, we demonstrated that Self-mediated regulation of cellular redox status was primarily derived from its subsequent effects on ER stress. Together, our results suggest that SelK protects skeletal muscle from damage and is a crucial regulator of myogenesis.

Highlights

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  Selenoprotein K expression was upregulated in activated satellite cells.

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  Selenoprotein K silence impaired skeletal muscle regeneration and myogenic differentiation.

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  Selenoprotein K silence aggravated oxidative stress and endoplasmic reticulum stress.

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  Selenoprotein K regulated ROS production by stabling endoplasmic reticulum stress.