Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease
By M. Grande, B. Sanchez-Laorden, Cristina López-Blau, Cristina, A. D. Frutos, A. Boutet, M. Arévalo, R. Rowe, Stephen, J. Weiss and 2 more. Nature Medicine, 2015
721 citations recorded by the source corpus.
Progressive kidney fibrosis contributes greatly to end-stage renal failure, and no specific treatment is available to preserve organ function. During renal fibrosis, myofibroblasts accumulate in the interstitium of the kidney, leading to massive deposition of extracellular matrix and organ dysfunction. The origin of myofibroblasts is manifold, but the contribution of an epithelial-to-mesenchymal transition (EMT) undergone by renal epithelial cells during kidney fibrosis is still debated. We show that the reactivation of Snai1 (encoding snail family zinc finger 1, known as Snail1) in mouse renal epithelial cells is required for the development of fibrosis in the kidney. Damage-mediated Snail1 reactivation induces a partial EMT in tubular epithelial cells that, without directly contributing to the myofibroblast population, relays signals to the interstitium to promote myofibroblast differentiation and fibrogenesis and to sustain inflammation. We also show that Snail1-induced fibrosis can be reversed in vivo and that obstructive nephropathy can be therapeutically ameliorated in mice by targeting Snail1 expression. These results reconcile conflicting data on the role of the EMT in renal fibrosis and provide avenues for the design of novel anti-fibrotic therapies.
Subfields: Molecular Biology, Nephrology, Surgery
View Paper: https://www.semanticscholar.org/paper/0a339279c2a954c4bdc464dcad8583c2e818b698
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Citations in the corpus
- TGF-β1 Signaling and Tissue Fibrosis. (2018, background): “In models of kidney fibrosis, epithelial-specific deletion of the genes encoding the EMT transcription factor Snail1 or Twist leads to attenuated fibrosis (Grande et al. 2015; Lovisa et al. 2015).”
- Kidney fibrosis: from mechanisms to therapeutic medicines (2023, background): “Later, partial EMT has been proposed, which indicated that dedifferentiated tubules do not fully translate into myofibroblasts, but exacerbated kidney fibrosis via the secretion of mediators to trigger the differentiation of myofibroblast.(52,54)”