Abstract
Viper bite envenoming often results in prominent skeletal muscle damage. According to our previous studies, the prolonged presence of Crotalus atrox venom toxins induced extensive muscle damage, which mimicked the outcome of chronic muscle damage often seen in human muscular dystrophies. In the case of chronic muscle damage, two critical processes occur: muscle regeneration is impaired, and fibrosis develops. Myostatin/activin signalling is a key regulator of both of these processes. Myostatin and its closely related molecules, in particular activin, inhibit the proliferation and differentiation of myocytes while promoting proliferation of fibroblasts and expression of extracellular matrix proteins. Thus, attenuating myostatin/activin signalling offers an attractive means of promoting muscle development while decreasing fibrosis. Hence, we have used the soluble activin receptor type IIb, which acts as a ligand trap for both myostatin and activin, to dampen signalling and assessed whether this intervention could alter the pathological trajectory of C. atrox venom-induced muscle damage in mice. We report that the soluble activin receptor type IIb treatment increased the size of regenerating fibres while reducing the level of fibrotic tissues in venom-damaged muscle.