| Summary: | The use of ionic metals such as zinc (Zn<sup>2+</sup>) is providing promising results in regenerative medicine. In this study, human keratinocytes (HaCaT cells) were treated with different concentrations of zinc chloride (ZnCl<sub>2</sub>), ranging from 1 to 800 µg/mL, for 3, 12 and 24 h. The results showed a time–concentration dependence with three non-cytotoxic concentrations (10, 5 and 1 µg/mL) and a median effective concentration value of 13.5 µg/mL at a cell exposure to ZnCl<sub>2</sub> of 24 h. However, the zinc treatment with 5 or 1 µg/mL had no effect on cell proliferation in HaCaT cells in relation to the control sample at 72 h. The effects of the Zn<sup>2+</sup> treatment on the expression of several genes related to glycoprotein synthesis, oxidative stress, proliferation and differentiation were assessed at the two lowest non-cytotoxic concentrations after 24 h of treatment. Out of 13 analyzed genes (superoxide dismutase 1 (<i>SOD1)</i>, catalase <i>(CAT)</i>, matrix metallopeptidase 1 <i>(MMP1),</i> transforming growth factor beta 1 <i>(TGFB1)</i>, glutathione peroxidase 1 (<i>GPX1),</i> fibronectin 1 (<i>FN1)</i>, hyaluronan synthase 2 <i>(HAS2)</i>, laminin subunit beta 1 <i>(LAMB1),</i> lumican <i>(LUM)</i>, cadherin 1 (<i>CDH1)</i>, collagen type IV alpha <i>(COL4A1)</i>, fibrillin (<i>FBN)</i> and versican <i>(VCAN</i>)), Zn<sup>2+</sup> was able to upregulate <i>SOD1, CAT, TGFB1, GPX1, LUM, CDH1, FBN</i> and <i>VCAN</i>, with relative expression levels of at least 1.9-fold with respect to controls. We found that ZnCl<sub>2</sub> promoted glycoprotein synthesis and antioxidant gene expression, thus confirming its great potential in biomedicine.
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