TGFß signaling: its role in fibrosis formation and myopathies.

ABSTRACT

PURPOSE OF REVIEW Modifiers of TGFß signaling have been investigated as treatment options for several types of muscle diseases. The purpose of this review is to focus on the most recent studies that have used this treatment strategy for pathological muscle disorders. We also review the recent insight into the mechanistic processes by which TGFß signaling contributes to these pathologies by promoting fibrosis formation. RECENT FINDINGS: Recent research has shed light on the role of TGFß signaling in the regulation of microRNAs associated with fibrosis formation. Inhibition of TGFß signaling by Losartan treatment greatly improved the phenotype of myopathies associated with laminin-α2-deficient congenital muscular dystrophy. Caveolin 3 deficiency was also ameliorated by the use of several different types of TGFß signaling inhibitors. Use of Losartan had dramatically beneficial effects on sarcopenic muscle by improving the regeneration after injury. Pharmacological manipulation to increase muscle mass is an emerging trend in obesity treatment research. New advances in the use of potent myostatin inhibitors have made this an attractive approach for future studies. SUMMARY: An increasing number of skeletal myopathies are demonstrating favorable responses to alterations of the TGFß signaling pathway. However, future research is needed to fully understand the downstream molecular signature associated with this pathway in order to develop more specific targeted therapies.