[en] Rheumatoid arthritis (RA) is an inflammatory, chronic and autoimmune joint disease that affects approximately 1% of the population. Its therapeutic strategy is based on drugs aimed at reducing inflammation of the joints; however, due to the chronic nature of this disease, these treatments have significant side effects, and a high cost. This has motivated an increase in the study of the therapeutic potential of natural antioxidants such as resveratrol (RSV), as new and complementary treatment opportunities. Previously, our group has shown that oral supplementation of RSV could reduce the main signs of the pathology of RA, such as a reduction in synovial hyperplasia, immune infiltrate in the joint and the production of inflammatory mediators, in addition to the stress and oxidative damage typical of an arthritic joint, thus preventing disease progression. Carrying on with this study, the aim of this proyect was to evaluate in an in vivo antigen-induced arthritis model (AIA) if the RSV is able to modulate the expression of the Nrf2 transcription factor, which has emerged as the most important mechanism transcription involved in the increased expression of antioxidant genes and in maintaining the redox balance; as well as angiogenesis and autophagy processes, key mechanisms in controlling abnormal proliferation that characterizes RA synovium. Furthermore, in vitro analysis by silencing Nrf2 transcription factor in synoviocytes was performed to evaluate its involvement in controlling the inflammatory response and if the RSV exerts the protective effect by inducing Nrf2. The results showed that RSV was able to activate Nrf2 transcription factor, and modulate the expression of autophagic and angiogenic markers. This suggests that RSV is able to modulate synovial hyperplasia increasing autophagic cell death, and limiting the angiogenic process, and supports the use of RSV as a new therapeutic strategy in the treatment of RA.

[gl] A artrite reumatoide (AR) é una doenza inflamatoria e crónica de carácter autoinmune que afecta aproximadamente ó 1% da población mundial. A súa estratexia terapéutica basase en fármacos dirixidos a reducir a inflamación das articulacións; sin embargo, debido ó carácter crónico desta doenza, ditos tratamentos teñen importantes efectos adversos, ademais dun custo elevado. Isto ha motivado un gran auxe no estudio do potencial terapéutico de antioxidantes naturais, como o resveratrol (RSV), como novas e complementarias oportunidades de tratamento. Previamente, noso grupo ha demostrado que a suplementación oral de RSV podería reducir os principais signos da patoloxía da AR, como son una reducción da hiperplasia sinovial, do ilfiltrado inmune na articulación y da producción de mediadores inflamatorios, ademáis do estrés e daño oxidativo típicos dunha articulación artrítica, previniendo así a progresión da enfermidade. Continuando con este estudo, o obxectivo deste traballo foi avaliar nun modelo in vivo de artrite inducida por antíxeno (AIA) se o RSV é capaz de modular a expresión do factor de transcripción Nrf2, que se ha erixido como o más importante mecanismo de transcripción implicado no incremento da expresión de xenes antioxidantes e no mantemento do equilibrio redox; así coma os procesos de anxioxénese e autofaxia, mecanismos claves no control da proliferación anormal que caracteriza o texido sinovial AR. Así mesmo, mediante análise in vitro realizouse o silenciamento do factor de transcripción Nrf2 en sinoviocitos para avaliar a súa implicación no control da respuesta inflamatoria e si o RSV exerce o efecto protector a través da inducción de Nrf2. Os resultados desmostraron que o RSV foi capaz de activar o factor de transcripción Nrf2, e modular a expresión de marcadores autofáxicos e anxioxénicos. Todo isto suxire que o RSV é capaz de modular a hiperplasia sinovial incrementando a norte celular por autofaxia, e limitanto o proceso anxioxénico, e apoya o uso de RSV como unha nova estratexia terapéutica no tratamento da AR.