Se-methylselenocysteine stimulates migration and antioxidant response in HaCaT keratinocytes: Implications for wound healing

Background: Se-methylselenocysteine (MSC), a natural organic selenium compound, is known for its anticancer effects. In the present study, we investigated the effects of MSC on cell migration, which is the most limiting step in the reepithelialization process of wound healing and the antioxidant response in HaCaT keratinocytes. Methods: HaCaT cells were treated with various concentrations of MSC. Cell migration and proliferation, the expression of proteins that are involved in the epidermal-mesenchymal transition (EMT) process, the extent of oxidative stress and the antioxidant response, and the associated signaling pathways were analyzed. Results: MSC (100-500 mu M) increased HaCaT cell migration. MSC stimulated EMT, which was evidenced by a decrease in E-cadherin in the cells at the wound edge and increases in Snail, Twist, and matrix metalloproteinases. MSC increased the phosphorylation of Akt and glycogen synthase kinase 3 beta, which led to the stabilization and nuclear accumulation of beta-catenin, a transcriptional coactivator involved in EMT. MSC caused a transient increase and then an eventual decrease in cellular reactive oxygen species, which appeared to be associated with the increase in nuclear factor erythroid 2-related factor 2, a key transcription factor for the antioxidant response. Conclusion: Our results suggest that MSC can promote skin wound healing by stimulating keratinocyte migration and, moreover, can protect cells from excessive oxidative stress that often accompanies and impairs the wound healing process, particularly in chronic wounds, by stimulating an antioxidant response.