The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration

Abstract

Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential.

Keywords: Piezo1; Yoda1; muscle atrophy; myoblasts; myogenesis; myotubes; sarcopenia; satellite cells.

Figure 1

Role of Piezo1 in skeletal muscle. (A), Piezo1 controls the adult myogenesis. (a) Quiescent satellite cells (MuSCs) are located on intact muscle fibers. (b) Under muscle injury or following the Piezo1 activation by Yoda1, the MuSCs shift toward a G_Alert phase favouring the cell activation. (c) Part of the MuSCs self-renews the quiescent population; (d) the rest proliferates as myoblasts, differentiate into myocytes, which then fuse into multinucleated myotubes. The pharmacological activation of Piezo1 by Yoda1 promotes myocyte fusion and myotube differentiation. (B), A down regulation of PIEZO1 expression leads to disuse atrophy of the adult muscle. (C), The stimulation of the Piezo1 activity of endothelial cells and muscle cells during physical exercise sustain angiogenesis and muscle trophism.

Figure 2

Potential Piezo1-based therapeutic strategies to counteract skeletal muscle impairments. Muscle disuse, aging and unloading might reduce Piezo1 activity, contributing to muscle atrophy and poor blood supply. Potentiation of Piezo 1 activity by physical exercise, diet and chemical/pharmacological activation might enhance the regenerative potential and, possibly, skeletal muscle vascularization and provide a higher blood supply. DHA and ceramide are lipids which are able to enhance the activity of Piezo1 channels, reducing their limiting inactivation state. These indirect and more direct Piezo1-based therapeutic strategies based on novel mechanisms of Piezo1 activation could thus represent promising new countermeasures versus atrophy and diseases related to muscle weaknesses (Figure created with Biorender.com, accessed on 2 May 2022).