The following is a summary of “FGF4 Promotes Skin Wound Repair through p38 MAPK and GSK3β-Mediated Stabilization of Slug,” published in the June 2023 issue of Investigative Dermatology by Sun et al.

Restoring the barrier function and structural integrity of injured skin, cutaneous wound healing is an orderly and complex process. Re-epithelialization, which entails the proliferation and migration of keratinocytes to cover the denuded surface, is essential for wound healing. Numerous members of the FGF family have been identified as positive regulators of wound repair, including the paracrine-acting FGF1 and FGF7 subfamily members. 

Nonetheless, the function and underlying mechanisms of a few other paracrine FGFs in wound healing remain unknown. Paracrine FGF4 localized predominantly to epidermal keratinocytes and was significantly upregulated at the wound edges in response to re-epithelialization in human and mouse wound models, as described in this study. Human ex vivo cutaneous wounds re-epithelialized more slowly when FGF4 was inhibited, whereas recombinant FGF4 treatment promoted re-epithelialization and wound repair.

Mechanistically, recombinant FGF4 promotes p38 MAPKGSK3mediated stabilization of Slug by reducing its ubiquitination, which triggers epithelial-to-mesenchymal transition and stimulates the migration and proliferation of keratinocytes, thereby promoting lesion re-epithelialization. The researchers’ findings identify FGF4 as an essential wound-healing regulator, emphasizing a promising therapeutic avenue for skin injuries.

Source: sciencedirect.com/science/article/abs/pii/S0022202X22028457