The TWEAK-Fn14 pathway: A potent regulator of skeletal muscle biology in health and disease

TNF-like weak inducer of apoptosis (TWEAK), a TNF superfamily ligand, and its bona fide receptor, the TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14), represent a pivotal axis for shaping both physiological and pathological tissue responses to acute or chronic injury and disease. In recent years significant advances have been made in delineating the prominent role of TWEAK-Fn14 dyad in regulating skeletal muscle mass and metabolism. Also emerging from the broad study of tissue injury in skeletal muscle and other organs is the role of the TWEAK-Fn14 pathway in promoting fibrosis. This review article highlights recent advancements toward understanding how the TWEAK-Fn14 pathway regulates the response to various skeletal muscle insults and, more broadly, engages multiple mechanisms to drive tissue fibrosis.