A mechanism of melanogenesis mediated by E‐cadherin downregulation and its involvement in solar lentigines

Objective Intensive 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. Methods First, 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. Results E‐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. Conclusion Our 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. Abstrait Objectif Des études intensives ont révélé que les facteurs mélanocytaires pléiotropiques sont associés à la formation de taches de vieillesse. On pense que la différenciation des kératinocytes dysfonctionnels est une cause en amont de la formation des taches de vieillesse. Bien qu’il ait été démontré que la différenciation des kératinocytes est médiée par le facteur de contact cellule‐cellule E‐cadhérine, son implication dans la formation des taches de vieillesse reste inconnue. Ainsi, pour déterminer l’origine des taches de vieil