Fibroblast growth factor-inducible 14 signalling pathway in cutaneous wounds: a potential therapeutic target

Cutaneous wound healing consists of complex processes involving different types of cells and signalling pathways, and occurs in three phases (inflammatory, proliferative and tissue remodelling). The dysregulation of these processes leads to abnormal wound healing, manifesting as hard-to-heal (chronic) wounds at one extreme and pathological scarring at the other. Recent studies have shown that the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signalling pathway regulates inflammatory, re-epithelialisation, collagen synthesis and angiogenesis processes, suggesting that it can modulate cutaneous wound healing. Despite numerous studies suggesting a relationship between the TWEAK/Fn14 axis and cutaneous wound healing, there has been little attention paid to this relationship to date. There is scarce direct evidence supporting that TWEAK/Fn14 axis-targeted therapies work in cutaneous wounds. This review summarises the evidence that TWEAK/Fn14 signalling is involved in wound repair as well as in tissue remodelling. In addition, TWEAK/Fn14 axis-targeted therapies in other diseases are highlighted, and their therapeutic potential in cutaneous wounds discussed.