RESUMO
Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.
Assuntos
Expressão Gênica/efeitos dos fármacos , Glicerol/farmacologia , Queratinócitos , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Xilitol/farmacologia , Sobrevivência Celular , Proteínas Filagrinas , Antígenos HLA-DR/genética , Humanos , Interleucinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Proteína Quinase C-delta/metabolismo , Transporte Proteico/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
The authors present the case of a multiplex endocrine neoplasia type 2A (MEN2A). The 55-year-old woman underwent detailed examinations for abdominal complaints. Bilateral adrenal masses and thyroid nodular goiter were found. Based on metanephrine excretion and MIBG imaging, bilateral phaeochromocytomas were diagnosed. The thyroid nodules were confirmed by thyroidectomy as bilateral medullary thyroid carcinoma. Asymptomatic primary hyperparathyroidism was also detected. Laparoscopic adrenalectomy and parathyroid adenoma removal were performed. Based on family history and the characteristic clinical presentation, MEN2A syndrome was confirmed by genetic testing. During genetic screening of first-degree relatives, the patient's 25-year-old daughter was shown to be a gene carrier. Preventive thyroidectomy was performed and histology proved multifocal medullary thyroid cancer. In addition to the importance of genetic testing, the authors emphasize the guideline-based, but individualized approach to patients with suspected MEN2A syndrome. Orv Hetil. 2020; 161(2): 75-79.