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

OBJECTIVE:The 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. METHODS:Keratinocytes 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. RESULTS:EMILIN-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. CONCLUSION:The 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.