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

The regeneration of adult skeletal muscle after injury is primarily initiated by satellite cells (SCs), but the reg-ulatory 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 devel-opment 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.

Automated summary

This study reveals the important role of SelK in skeletal muscle myogenesis. Loss of SelK delays skeletal muscle regeneration and inhibits the development of myoblasts into myotubes. In addition, SelK deficiency leads to increased cellular stress, oxidative stress, autophagy, and apoptosis. Supplementation with specific inhibitors partially restores the differentiation potential and formation of myotubes.