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Comprehensive Analysis of Zinc Derivatives Pro-proliferative, Anti-Apoptotic and Antimicrobial Effect on Human Fibroblasts and Keratinocytes in a Simulated, Nutrient-deficient Environment In Vitro
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Julian-Dario Rembe    1, Julia Katharina Boehm2 , Carolin Fromm-Dornieden2 , Nina Hauer3 , Ewa Klara Stuermer4 |
1- Department of Vascular and Endovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany. , julian-dario.rembe@uni-wh.de
2- Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University.
3- Chair for Translational Wound Research, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University.
4- Department of Vascular Medicine, University Heart Center, Translational Wound Research, University Medical Center Hamburg-Eppendorf. |
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Abstract: (4077 Views) |
| Zinc as therapeutic agent in skin and wound care has been known for centuries, but its role is controversial and comprehensive investigations in nutrient-deficient environments are lacking. We aimed to provide a broad analysis of different zinc derivatives on proliferation, apoptosis and antimicrobial properties in a simulated nutrient-deficient environment in vitro. Human fibroblasts (CRL2522) and keratinocytes (HaCaT) were treated with a broad concentration range (10 – 0.0001 µg/mL) of zinc-sulfate (ZnSO4), -gluconate (ZnGluc) and -histidine (ZnHis) for 1-6 days under nutrient-deficient media conditions. Cell proliferation was investigated by XTT assay. Targeted analyzes in proliferation (E2F1, PCNA) and apoptosis (TP53) associated genes were performed via qRT-PCR and apoptosis was determined via FACS (annexin V/7-AAD staining). Antimicrobial efficacy was investigated using a quantitative suspension method against S. aureus, P. aeruginosa, E. coli, and C. albicans. The results indicated that 0.1 to 0.001 µg/mL Zn increased cell proliferation in both cell lines. Fibroblasts were more susceptible with significant proliferation peaks on days 2 & 6, and days 1 & 4 for keratinocytes. No relevant changes in gene expression were detected for E2F1 and PCNA nor for TP53. Annexin-V/7-AAD-staining of fibroblasts revealed a small, yet insignificant reduction of apoptosis induction for ZnGluc and ZnSO4. ZnGluc and ZnSO4 (0.1%) achieved high microbial reductions (4-5 log10 reductions) against tested pathogens. ZnGluc and ZnSO4 showed relevant pro-proliferative and antimicrobial, as well as tendential anti-apoptotic features in a simulated nutrient-deficient microenvironment in vitro. This further validates a potential benefit of local zinc treatment in deficient wound microenvironments. |
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| Keywords: Wound healing, zinc, fibroblasts, keratinocytes, antimicrobial efficacy, cell proliferation, apoptosis |
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Full-Text [PDF 1013 kb]
(1800 Downloads)
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Type of Study: Original Article |
Subject:
Cell Biology
Received: 2020/03/16 | Accepted: 2020/07/7 | Published: 2020/06/30
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