title: Tilapia Piscidin 4 (TP4) Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice.
abstract: Antimicrobial peptides (AMPs) are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4), was isolated from Nile tilapia (Oreochromis niloticus); TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT) and fibroblast cell line (Hs-68). In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF) gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF), transforming growth factor (TGF), and vascular endothelial growth factor (VEGF). The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.
authors.affiliation: Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road, Jiaushi, Ilan 262, Taiwan. henryhw910@yahoo.com.tw.
authors.forename: Hang-Ning
authors.initials: HN
authors.lastname: Huang
authors.affiliation: Department of Life Science, Chinese Culture University, Taipei, Taiwan. phd.elainechan@gmail.com.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chan
authors.affiliation: Department of Food Science, National Taiwan Ocean University, 2, Pei-Ning Road, Keelung, Taiwan. cjwu@mail.ntou.edu.tw.
authors.forename: Chang-Jer
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road, Jiaushi, Ilan 262, Taiwan. zoocjy@gate.sinica.edu.tw.
authors.forename: Jyh-Yih
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity; D051379:Mice; D017210:Tilapia / Q000378:metabolism*; D015291:Transforming Growth Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D024061:Collagen Type III; D042461:Vascular Endothelial Growth Factor A; D051523:Fibroblast Growth Factor 7; D004815:Epidermal Growth Factor; D007633:Keratins; D015291:Transforming Growth Factors