Novel Fejervarin peptides promote acute and chronic skin wound healing

The skin wound healing process is complicated and vulnerable to factors such as accidental injury, microbial infection, skin diseases and metabolic dysfunction. Amphibian skin peptides have great potential in the treatment of acute and chronic skin wounds. We firstly cloned a novel group of bioactive peptides from frog Fejervarya moodiei and F. multistriata, showing no amino acid sequence similarities with known bioactive peptides, which is named as Fejervarin (Fej). Mature Fej-1a, Fej-1b, Fej-1c and Fej-1d are composed of 8 amino acid residues, including 2 or 3 negative amino acid residues, with -1 or -2 net negative charges under physiological conditions. In vitro, the Fej peptides significantly promoted proliferation and migration of RAW264.7, HaCaT and HSF cells assessed by CCK-8, EdU proliferation and scratch assays. In vivo, they exhibited the efficacy on promoting acute and chronic skin wound healing on mouse models of full-thickness skin injury and second-degree deep scald, after the mice were treated for 12 and 21 days, respectively. MASSON and H&E stains showed that in the peptide treated group, fibroblasts were formed; inflammation was relieved and the wounds were completely covered by the newly generated epidermis. IHC, WB and RT-PCR assays revealed that the Fej peptides up-regulated EGF and TGF-β expressions to promote the proliferation and migration of epithelial keratinocytes and skin fibroblasts. Collectively, the Fej peptides are promising multifunctional wound healing peptides to reshape the damaged tissue environment, providing effective alternative candidates for the repair and regeneration of acute and chronic cutaneous wounds.