Novel Antimicrobial Protein Fibroblast Growth Factor 8 Accelerates Skin Wound Healing via Directly Inhibiting Bacteria and Activating Glycolysis

Abstract Repairing and preventing infections of skin wounds are crucial for the body health. Fibroblast growth factors (FGFs) have functions of repairing skin wounds, while antimicrobial peptides/proteins (AMPs) can prevent the infections of skin. Therefore, if FGFs can act like AMPs, they will have better application potential in promoting skin wound healing. Here, it is found that grass carp fibroblast growth factor 8a (gcFGF8a) has broad‐spectrum and potent antibacterial activity through disrupting the cell membrane, indicating that FGF8 is an uncovered AMP. Further study revealed that gcFGF8a can accelerate skin wound healing through dual functions: inhibiting bacterial and activating of glycolysis. Mechanistically, gcFGF8a/FGFR4 signaling induces epithelial cell glycolytic programs for barrier remodeling through the mTORC1/HIF1α pathway. Interestingly, it is found that mouse FGF8b (mFGF8b), the homolog of gcFGF8a, also has antibacterial and skin wound repair activities, indicating that FGF8 is a functionally conserved molecule in vertebrates. To the knowledge, FGF8 is the only member of the FGF family with both antibacterial and wound repair functions at present, greatly enriching the understanding of this pivotal molecule. Furthermore, these findings highlighted the potential application of FGF8 as a skin wound repair drug.