Elastin microfibril interface‐located protein 1 in fibroblasts is regulated by amphiregulin and interleukin‐1α produced by keratinocytes

Abstract

AbstractObjectiveThe structure of elastic fibres changes with ageing. Elastin microfibril interface–located protein 1 (EMILIN‐1) is known to contribute to structural changes in elastic fibres. EMILIN‐1 is one of the components of elastic fibres and also colocalizes with oxytalan fibres near the epidermis. Therefore, EMILIN‐1 may be affected by epidermal–dermal interactions. The purpose of this study is to identify the key factors involved in epidermal–dermal interactions during the structural degeneration of elastic fibres.MethodsKeratinocytes and fibroblasts were co‐cultured, and changes in elastic fibre‐related proteins were evaluated. Additionally, cytokine arrays were used to identify the factors involved in epidermal–dermal interactions.ResultsEMILIN‐1 expression in fibroblasts was increased in the presence of keratinocytes, and its expression decreased when keratinocytes were stressed. Amphiregulin (AREG) and interleukin‐1α (IL‐1α) were identified as the keratinocyte‐derived cytokines that influence the production of EMILIN‐1, which is secreted by the fibroblasts. EMILIN‐1 expression was promoted by AREG and decreased by IL‐1α via an increase in cathepsin K (a catabolic enzyme). AREG and IL‐1α were associated with changes in EMILIN‐1 levels in fibroblasts.ConclusionThe findings suggest that the suppression of IL‐1α expression and promotion of AREG expression in the epidermis could be a new approach that prevents the wrinkles and sagging caused by the structural changes in elastic fibres.