RESUMEN
Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor ß1 (TGF-ß1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-ß1-induced expression of procollagen type 1 in keloid fibroblasts (p < 0.05). Moreover, it inhibited the TGF-ß1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase (p < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-ß1-induced fibrosis (p < 0.05). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.
Asunto(s)
Fibroblastos/metabolismo , Queloide/tratamiento farmacológico , Queloide/metabolismo , Oligopéptidos/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Adiponectina/farmacología , Adiponectina/uso terapéutico , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cicatriz/tratamiento farmacológico , Cicatriz/metabolismo , Colágeno Tipo I/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibrosis , Técnicas de Silenciamiento del Gen , Humanos , Inyecciones Intralesiones , Ratones , Ratones Desnudos , Oligopéptidos/administración & dosificación , Fosforilación , Proteínas Quinasas/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Proteína smad3/metabolismo , Trasplante HeterólogoRESUMEN
Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages and delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress in understanding the key features of this disease, the diagnosis of early-stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histologic findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful. In this review, we have summarized our current understanding of this disease entity from articles that were published between 1969 and 2018. We have outlined clinical and dermoscopic features as well as pathologic and molecular findings regarding acral melanoma and have presented an algorithm for diagnosis. Understanding and integrating these characteristics may assist clinicians in the early detection of acral melanomas.