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Tilapia Piscidin 4 (TP4) Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice
Hang-Ning Huang1, Yi-Lin Chan2, Chang-Jer Wu3
1Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road, Jiaushi, Ilan 262, Taiwan. henryhw910@yahoo.com.tw.
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.
Insights
Tilapia piscidin 4 (TP4), an antimicrobial peptide, promotes wound healing and combats MRSA infections in mice. This peptide stimulates cell proliferation and tissue repair, suggesting its potential as a novel wound dressing agent.
Area of Science:
- Biochemistry
- Immunology
- Dermatology
Background:
- Antimicrobial peptides (AMPs) are crucial for innate immunity and possess diverse biological functions.
- Tilapia piscidin 4 (TP4), an AMP from Nile tilapia, exhibits antibacterial properties and modulates immune responses.
- The role of TP4 in wound healing and keratinocyte/fibroblast proliferation requires further investigation.
Purpose of the Study:
- To investigate the effects of TP4 on wound closure in mice.
- To analyze the impact of TP4 on keratinocyte (HaCaT) and fibroblast (Hs-68) cell proliferation.
- To evaluate the therapeutic potential of TP4 against MRSA infections and its toxicity profile.
Main Methods:
- In vitro assays assessing cell proliferation and gene expression (collagen I, III, KGF) in HaCaT and Hs-68 cells treated with TP4.
- In vivo studies using mouse models to assess TP4's efficacy against peritonitis and wound infections caused by MRSA.
- Toxicological evaluation of TP4 in mice, monitoring for adverse effects and organ toxicity.
Main Results:
- TP4 significantly stimulated proliferation and upregulated collagen I, collagen III, and KGF gene expression in Hs-68 cells at concentrations as low as 6.25 µg/mL.
- TP4 demonstrated high efficacy in combating MRSA-induced peritonitis and wound infections in mice.
- No adverse behavioral effects or liver/kidney toxicity were observed in TP4-treated mice.
Conclusions:
- TP4 enhances survival rates in MRSA-infected mice through combined antimicrobial and wound closure activities.
- TP4-mediated wound healing involves growth factors like EGF, TGF, and VEGF, promoting tissue homeostasis.
- TP4 shows promise as a potential topical agent for wound dressing applications.
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