Abstract
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-β 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-β signaling restricts the understanding of its roles in healing and wound chronification. Historically, low TGF-β 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-β 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-β in chronic wounds. In this review, we compile existing evidence on the roles played by TGF-β during skin wound healing, with special emphasis on keratinocyte responses. Current limitations and future perspectives of TGF-β research in chronic wounds are discussed.
Highlights
Chronic wounds are characterized by being unable to heal in an expected time frame
It is worth noting that accumulated evidence both in mice and humans corroborate the proposal of a prominent role of TGF-β2 in the regulation of hair follicle physiology [77,78,79,80]
While it is true that decreased TGF-β levels can be found in chronic wounds, a thorough review of aforementioned studies suggests that this statement would be rather inaccurate as it fails to convey the fact that high TGF-β levels are detected in the epidermis compartment
Summary
Chronic wounds are characterized by being unable to heal in an expected time frame. This is often related to defects in keratinocyte ability to epithelialize over recovered dermal tissue. Upon the eventual re-establishment of epithelial continuity, keratinocyte phenotype would revert to the initial state, completing the keratinocyte activation cycle [1] Alterations of this process could result in unsuccessful wound closure. Responses to its signaling range from damaged tissue repair, extracellular matrix (ECM) maintenance, epithelial and endothelial cell growth, and differentiation to the regulation of immune responses [6]. This constitutes an evolutionary wonder which introduces great difficulty in understanding some cellular behaviors at the molecular level. We aim to recapitulate useful evidence relevant to the issue, discussing current limitations and future perspectives in the research of TGF-β’s role in chronic wounds with a special focus on keratinocytes
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