TY - JOUR T1 - Resveratrol regulates ECM remodeling in lung fibrosis JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3914 AU - Nikica Mise AU - Isis E. Fernandez AU - Oliver Eickelberg Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3914.abstract N2 - Sirtuin 1 (SIRT1) is a protein deacetylases that is involved in regulation of cell metabolism, stress response and aging. Resveratrol, a polyphenol found in wines, it has been described as a potent activator of SIRT1 enzyme. Several studies have shown that resveratrol treatment can prevent progression of wide variety of age-associated diseases, including the pulmonary diseases. Therefore, we aim to investigate the mechanism by which SIRT1 might regulate the development and progression of lung fibrosis.Bleomycin-treated mice were gavaged with saline or with resveratrol daily. At the day 14 all mice were sacrificed, lung function was measured and lung tissues were excised and processed for further analysis. The results have shown increased survival rate of resveratrol-treated animals, as well as significantly improved lung function. Resveratrol treatment markedly reduced levels of fibrotic markers such as fibronectin, collagen I and collagen IV. Furthermore, our data have demonstrated that resveratrol treatment increased levels of autophagy markers LC3BII and Atg5. We have also shown that resveratrol-induced autophagy in human primary fibroblasts is SIRT1-dependent. Overexpression of SIRT1 in lung epithelial cells and fibroblast, increased expression of LC3BII and promoted formation of autophagosomes. Importantly, SIRT1 silencing led to increased deposition of extracellular matrix (ECM) proteins even in the presence of resveratrol.Taken together, these data provide evidences that resveratrol treatment decreases ECM deposition by regulation of autophagy and that this process is SIRT1-dependent. It is possible to hypothesize that SIRT1 expression and activity play a critical role during development of lung fibrosis. ER -