RESUMO
Human dermal fibroblasts (HDFs) are typically flattened or extensible shaped and play a critical role in the metabolism of extracellular matrix components. As the properties of fibroblasts in the dermis are considered to be influenced by their morphology, we investigated the morphological changes induced in fibroblasts by ultraviolet (UV) irradiation as well as the relationship between these changes and collagen metabolism. In this study, we showed that UVA exposure induced morphological changes and reduced collagen contents in HDFs. These morphological changes were accompanied a reduction in actin filaments and upregulation of the actin filament polymerization inhibitor, capping protein muscle Z-line É1 (CAPZA1). External actin filament growth inhibitors also affected the shape of HDFs and reduced collagen levels. These results suggest that UVA exposure may inhibit the polymerization of actin filaments and induce morphological changes in skin fibroblasts. These morphological changes in fibroblasts may accelerate reductions in collagen synthesis. This mechanism may be one of the processes responsible for collagen reductions observed in photoaged skin. When natural materials that suppress these morphological changes in HDFs were evaluated, we found that an extract of Lilium 'Casa Blanca' (LCB) suppressed UVA-induced alterations in the shape of HDFs, which are typically followed by inhibition of collagen reduction. An analysis of the active compounds in LCB extract led to the identification of regaloside I, which had a structure of phenylpropanoid glycerol glucoside, as the active compound inhibiting the upregulation of CAPZA1. Therefore, inhibition of UVA-induced morphological changes in HDFs is considered to be promising way for the suppression of collagen reduction in photoaging.
Assuntos
Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Pele/patologia , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Proteína de Capeamento de Actina CapZ/genética , Proteína de Capeamento de Actina CapZ/metabolismo , Forma Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Citocalasina D/farmacologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/efeitos da radiação , Expressão Gênica/efeitos dos fármacos , Humanos , Lilium , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/metabolismo , Envelhecimento da Pele/fisiologia , Tiazolidinas/farmacologiaRESUMO
Recently, it has been reported that increased expression of WNT1 accelerates the differentiation of melanocyte stem cells (McSCs) in solar lentigines (SLs), hyperpigmented maculae commonly seen on sun-exposed areas of the skin. In this study, to establish an in vitro SL model, human epidermal squamous carcinoma cell line HSC-1, which expresses higher levels of WNT1 than normal human epidermal keratinocytes, was co-cultured with early passage normal human epidermal melanocytes (NHEMs) as an in vitro McSC model. As a result, mRNA expression levels of melanocyte differentiation-related genes MITF and TYR in NHEMs were significantly increased by co-culturing with HSC-1 cells. Furthermore, Phalaenopsis orchid extract (Phex) inhibited McSCs differentiation by suppressing WNT1 expression via down-regulation of DLX2, a transcriptional activator of WNT1, in HSC-1 cells. Therefore, our finding suggested that extracts such as Phex, which suppresses WNT1 expression, may be useful as a novel treatment of SLs.