ObjectiveIntensive studies have revealed that pleiotropic melanocytic factors are associated with age‐spot formation. Dysfunctional keratinocyte differentiation is thought to be an upstream cause of age‐spot formation. Although it has been shown that keratinocyte differentiation is mediated by the cell–cell contact factor E‐cadherin, its involvement in age‐spot formation remains unknown. Thus, to determine the origin of age‐spots and an integrated solution for the same, we focused on E‐cadherin expression in the present study.MethodsFirst, we assessed the solar lentigines in cutaneous and cultured cells by means of immunofluorescence staining. Following that, keratinocytes treated with siRNAs against E‐cadherin were co‐cultured with melanocytes, and the secreted factors were identified by means of proteomic analysis of the culture supernatants. We also performed quantitative PCR to assess melanogenesis activity and screen ingredients. For behavioural analysis of melanocytes, we performed time‐lapse imaging using confocal laser scanning microscopy.ResultsE‐cadherin expression was downregulated in the epidermis of the solar lentigines, suggesting its involvement in age‐spot formation. E‐cadherin knocked down keratinocytes not only promoted the secretion of melanocytic/inflammatory factors but also increased melanogenesis by upregulating the expression of melanogenesis factors. Furthermore, live‐imaging showed that the downregulation of E‐cadherin inhibited melanocyte dynamics and accelerated melanin uptake. Finally, we identified Rosa multiflora fruit extract as a solution that can upregulate E‐cadherin expression in keratinocytes.ConclusionOur findings showed that E‐cadherin downregulation triggers various downstream melanocytic processes, such as the secretion of melanocytic factors and melanogenesis. Additionally, we showed that the Rosa multiflora fruit extract upregulated E‐cadherin expression in keratinocytes.

Background: Intensive studies have revealed pleiotropic melanocytic factors for age spot formation. In particular, dysfunctional keratinocyte differentiation is thought to be an upstream cause of age spot formation. Although keratinocyte differentiation is mediated by a cell-cell contact factor, E-cadherin, its involvement in age spots remains unknown. To find the origin of age spots and an integrated solution, we focused on E-cadherin. Methods: Immunofluorescent staining with cutaneous tissues and cultured cells was performed. Keratinocytes treated with siRNAs were cocultured with melanocytes. With the supernatants of the keratinocyte culture, secretion factors were identified using proteomic analysis. For the activity of melanogenesis and the ingredient screening, a quantitative PCR was performed. For the behavioral analysis of melanocytes, time-lapse imaging of melanocytes was done by confocal laser scanning microscopy. Results: In age spots, E-cadherin expression in the epidermis was downregulated, suggesting that E-cadherin is implicated in age spot formation. E-cadherin knockdown (E-cad-KD) keratinocytes not only promoted the secretion of melanocytic/inflammatory factors, but also increased melanogenesis by upregulating the expression of melanogenesis factors. Furthermore, live imaging showed E-cadherin downregulation detained melanocyte dynamics and accelerated melanin-uptake. Finally, we identified Rosa multiflora fruit extract as a solution for upregulating E-cadherin in keratinocytes. Conclusion: Our findings showed that E-cadherin downregulation triggers various downstream melanocytic processes such as secretion of melanocytic factors and melanogenesis. Additionally, we showed that Rosa multiflora fruit extract upregulates E-cadherin expression in keratinocytes.