Browsing by Author "Frutos, Cristina A. de"
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Item Snail1 factor behaves as a therapeutic target in renal fibrosis.(Nature Medicine, 2015) Grande Rodríguez, Mª Teresa; López Blau, Cristina; Sánchez Laorden, Berta; Frutos, Cristina A. de; Boutet, Agnès; Grant Rowe, R.; Weiss, Stephen J.; López Novoa, José M.; Nieto, M. AngelaKidney fibrosis is a devastating disease that leads to organ failure, and no specific treatment is available to preserve organ function. In fibrosis, myofibroblasts accumulate in the interstitium leading to massive deposition of extracellular matrix and organ disfunction. The origin of myofibroblasts is multiple and the contribution of renal epithelial cells after undergoing epithelial-to-mesenchymal transition (EMT) is still debated. In a model unable to reactivate the EMT inducer Snail1 upon damage, we show that Snail1 is required in renal epithelial cells for the development of fibrosis. Damage-mediated Snail1 reactivation induces a partial EMT that relays fibrotic and inflammatory signals to the interstitium through the activation of TGF-β and NF-B pathways. Snail1-induced fibrosis can be reverted in vivo and inhibiting Snail1 in a model of obstructive nephropathy highly ameliorates fibrosis. These results reconcile conflicting data on the role of EMT in renal fibrosis and provide avenues for the design of antifibrotic therapies.