RESUMO
Solar ultra-violet (UV) radiation and the ensuing photo-damage are adverse factors affecting human skin directly exposed to the sun. Stress responses induced by UV radiation (UVR) elicit premature skin ageing (photoageing), resulting in extensive damage to dermal connective tissue. Disruption of the normal dermal structure of skin connective tissue, primarily collagen, impairs a variety of skin functions and is considered to be the main cause of wrinkle formation. Matrix metalloproteases (MMPs) may be responsible for the degradation of collagen and other extracellular matrix proteins, which are major targets for relieving skin photoageing. Herein, we demonstrated that Sirt1, a putative anti-ageing enzyme, reduced MMP-9 transcriptional expression in skin. The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR. These studies suggest that the Sirt1 activator could be used as a novel therapeutic agent to delay skin photoageing.
Assuntos
Regulação Enzimológica da Expressão Gênica/fisiologia , Metaloproteinase 9 da Matriz/metabolismo , Sirtuína 1/metabolismo , Pele/metabolismo , Animais , Biocatálise/efeitos dos fármacos , Biocatálise/efeitos da radiação , Células Cultivadas , Colágeno Tipo IV/metabolismo , Derme/citologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Expressão Gênica/efeitos da radiação , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Metaloproteinase 9 da Matriz/genética , Metformina/farmacologia , Camundongos , Camundongos Pelados , Resveratrol , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/genética , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Estilbenos/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Raios UltravioletaRESUMO
S-Methylmethionine sulfonium (SMMS) is a derivative of the amino acid methionine, and is synthesized in a variety of plants. SMMS is widely referred to as vitamin U because of its potent therapeutic effect on gastrointestinal ulceration. Skin wounds are accompanied by mucosal erosion and share similar histopathological aspects with gastric ulcers, so it is plausible that SMMS may promote skin wound healing. In animal models, topical administration of SMMS for a given period of time, to both physical and chemical wounds, facilitated wound closure and promoted re-epithelialization compared with a control. In addition, single SMMS treatment was sufficient to promote the growth of human dermal fibroblasts (hDFs) as well as the migration of hDFs, which are indispensable steps for skin wound healing. The promotion of hDF proliferation and migration resulted from considerable activation of ERK1/2 by SMMS, and inhibition of ERK activity by a chemical inhibitor significantly abrogated both the promoted proliferation and migration of hDFs. Therefore, we concluded that SMMS facilitated the repair process of skin damage by activation of dermal fibroblasts, which suggests that SMMS has potential as a skin wound-healing agent.
