Molecular events underlying maggot extract promoted rat in vivo and human in vitro skin wound healing

Maggot extracts promote wound healing, but their bioactive part(s) and molecular effects on the regenerating tissues/cells remain largely unclear. These issues are addressed here by treating rat skin wounds, human keratinocyte line/HaCat and fibroblasts with maggot secretion/excretion, and the extracts of maggots without and with secretion/excretion. The wound closure rates, cell proliferation activities, and statuses of wound healing‐related signaling pathways (STAT3, Notch1, Wnt2, NF‐κB, and TGF‐beta/Smad3) and their downstream gene expression (c‐Myc, cyclin D1, and VEGF) are evaluated by multiple approaches. The results reveal that the maggot extracts, especially the one from the maggots without secretion/excretion, show the best wound healing‐promoting effects in terms of quicker wound closure rates and more rapid growth of keratinocytes and fibroblasts. Of the five signaling pathways checked, the ones mediated by TGF‐beta/Smad3, and STAT3 are activated in the untreated wounds and become further enhanced by the maggot extracts, accompanied with c‐Myc, VEGF, and cyclin D1 up‐regulation. Our results thus show (1) that both body extract and secretion/excretion of maggots contain favorable wound healing elements and (2) that the enhancement of TGF‐beta/Smad3 and STAT3 signaling activities may be the main molecular effects of maggot extracts on the wound tissues.