Role of TGF-β signaling in inherited and acquired myopathies

TLDR

The TGF‑β superfamily, including TGF‑β1, MAPKs, and myostatin, regulates skeletal muscle growth, differentiation, regeneration, and stress response, but chronic elevation of these signals is linked to impaired regeneration and atrophy in neuromuscular disorders. This review examines aberrant TGF‑β signaling in disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical‑illness myopathy. The authors analyze how dysregulated TGF‑β signaling pathways contribute to the pathogenesis of these conditions. Inhibition of key TGF‑β pathway components has been shown to ameliorate disease phenotypes, suggesting new therapeutic opportunities for neuromuscular disorders.

Abstract

The transforming growth factor-beta (TGF-β) superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs), and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders.