Role of TGF-β in Skin Chronic Wounds: A Keratinocyte Perspective

Chronic wounds are characterized for their incapacity to heal within an expected time frame. Potential mechanisms driving this impairment are poorly understood and current hypotheses point to the development of an unbalanced milieu of growth factor and cytokines. Among them, TGF-beta is considered to promote the broadest spectrum of effects. Although it is known to contribute to healthy skin homeostasis, the highly context-dependent nature of TGF-beta signaling restricts the understanding of its roles in healing and wound chronification. Historically, low TGF-beta levels have been suggested as a pattern in chronic wounds. However, a revision of the available evidence in humans indicates that this could constitute a questionable argument. Thus, in chronic wounds, divergences regarding skin tissue compartments seem to be characterized by elevated TGF-beta levels only in the epidermis. Understanding how this aspect affects keratinocyte activities and their capacity to re-epithelialize might offer an opportunity to gain comprehensive knowledge of the involvement of TGF-beta in chronic wounds. In this review, we compile existing evidence on the roles played by TGF-beta during skin wound healing, with special emphasis on keratinocyte responses. Current limitations and future perspectives of TGF-beta research in chronic wounds are discussed.