Jennifer A Fernández-Rodríguez1, Maylin Almonte-Becerril1,2, Olalla Ramil-Gómez1, Laura Hermida-Carballo1, Susana Viñas-Diz1,3, Ángela Vela-Anero4, Ángel Concha5, María Camacho-Encina6, Francisco J Blanco6, María J López-Armada1. 1. Grupo de Investigación en Envejecimiento e Inflamación, SERGAS, Complexo Hospitalario Universitario A Coruña (CHUAC), Instituto de Investigación Biomédica A Coruña (INIBIC), Agrupación Estratégica CICA-INIBIC, As Xubias 84, A Coruña, 15006, Spain. 2. Universidad Intercultural Estado de Puebla, Calle Principal a Lipuntahuaca S/N, Lipuntahuaca, Puebla, 73475, México. 3. Departamento de Ciencias Biomédicas, Medicina y Fisioterapia, Universidade da Coruña (UDC), Campus de Oza, A Coruña, 15006, Spain. 4. Grupo de Terapia Celular e Medicina Regenerativa, UDC, Campus de Oza, A Coruña, 15006, Spain. 5. Servicio de Patología, INIBIC, SERGAS, As Xubias 84, A Coruña, 15006, Spain. 6. Grupo de Investigación en Reumatología, Agrupación Estratégica CICA-INIBIC, SERGAS, As Xubias, 84, A Coruña, 15006, Spain.
Abstract
SCOPE: Previous work reported that dietary supplementation with resveratrol lowers synovial hyperplasia, inflammatory and oxidative damage in an antigen-induced arthritis (AIA) model. Here, it is investigated whether resveratrol can regulate the abnormal synovial proliferation by inducing autophagy and controlling the associated inflammatory response. METHODS AND RESULTS: Animals treated with resveratrol 8 weeks before AIA induction show the highest significant signal for microtubule-associated protein 1 light chain 3 by confocal microscopy. Besides, resveratrol significantly reduces p62 expression, but it does not increase the signal of beclin-1. Also, active caspase-3 expression, as well as poly(ADP-ribose) polymerase, is upregulated in the AIA group, and is significantly reduced in resveratrol-treated AIA group. Resveratrol also mitigates angiopoietin-1 and vascular endothelial growth factor signals. Finally, resveratrol significantly reduces the serum levels of IL-1β, C reactive protein, and prostaglandin E2, as well as nuclear factor κB synovial tissue expression, which shows a significant correlation with p62 expression. CONCLUSION: Dietary supplementation with resveratrol induces the noncanonical autophagy pathway and limits the cross-talk with inflammation, which in consequence modulates the synovial hyperplasia. Preventive strategies that incorporate dietary intervention with resveratrol may offer a potential therapeutic alternative to drugs to influence the risk of rheumatoid arthritis and influence its course.
SCOPE: Previous work reported that dietary supplementation with resveratrol lowers synovial hyperplasia, inflammatory and oxidative damage in an antigen-induced arthritis (AIA) model. Here, it is investigated whether resveratrol can regulate the abnormal synovial proliferation by inducing autophagy and controlling the associated inflammatory response. METHODS AND RESULTS: Animals treated with resveratrol 8 weeks before AIA induction show the highest significant signal for microtubule-associated protein 1 light chain 3 by confocal microscopy. Besides, resveratrol significantly reduces p62 expression, but it does not increase the signal of beclin-1. Also, active caspase-3 expression, as well as poly(ADP-ribose) polymerase, is upregulated in the AIA group, and is significantly reduced in resveratrol-treated AIA group. Resveratrol also mitigates angiopoietin-1 and vascular endothelial growth factor signals. Finally, resveratrol significantly reduces the serum levels of IL-1β, C reactive protein, and prostaglandin E2, as well as nuclear factor κB synovial tissue expression, which shows a significant correlation with p62 expression. CONCLUSION: Dietary supplementation with resveratrol induces the noncanonical autophagy pathway and limits the cross-talk with inflammation, which in consequence modulates the synovial hyperplasia. Preventive strategies that incorporate dietary intervention with resveratrol may offer a potential therapeutic alternative to drugs to influence the risk of rheumatoid arthritis and influence its course.
Authors: Benrong Liu; Lihua Pang; Yang Ji; Lei Fang; Chao Wei Tian; Jing Chen; Changnong Chen; Yun Zhong; Wen-Chao Ou; Yujuan Xiong; Shi Ming Liu Journal: Front Cardiovasc Med Date: 2022-01-03