Abstract
Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6α (K6α) and inhibition of β-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of β-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of β-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.
Highlights
To validate wound conditions for both non-wound and wound groups on day 7, skin full-thickness was evaluated by woundinduced keratin (K6α wound marker) using immunofluorescence staining
ferulic acid (FA) treatment continued to increase the localization and expression of keratin 6α (K6α) on day 3 (Figure 2e,g). These results suggested that FA exerted similar wound healing effects to SH, modulating the downregulation of β-catenin and the upregulation of K6α, implying that FA modulated the expression of β-catenin and K6α at the wound edge and enhanced wound healing through the promotion of keratinocyte migration
We demonstrated that SH and FA treatment induced rapid wound closure in acute wounds and the migration of epidermal keratinocytes in ex vivo culture
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Wound healing is a dynamic biological process with complex, diverse interactions at the molecular level that are only partially understood. Many studies in recent decades have contributed to a better understanding of the mechanisms of the wound repair process and the causes and results of delayed wound healing. Acute wounds are still frequently reported to cause health trouble, with 11 million people suffering from wounds and approximately 300,000 patients hospitalized annually in the United States. Acute wounds are still frequently reported to cause health trouble, with 11 million people suffering from wounds and approximately 300,000 patients hospitalized annually in the United States. [1]
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