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Closed Access item Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney

Authors:Boutet, Agnès
Frutos, Cristina A. de
Maxwell, Patrick H.
Mayol, M. José
Romero, J.
Nieto, M. Ángela
Keywords:Cadherin-16, Epithelial–mesenchymal transition, HNF-1beta, Renal fibrosis, Snail transcription factors
Issue Date:Nov-2006
Publisher:Nature Publishing Group
Citation:Embo Journal 25(23): 5603-5613 (2006)
Abstract:During embryonic development, the kidney epithelium originates from cells that undergo a mesenchymal to epithelial transition (MET). The reverse process, epithelium to mesenchyme transition (EMT), has been implicated in epithelial tumor progression and in the fibrosis that leads to end-stage kidney failure. Snail transcription factors induce both natural and pathological EMT, but their implication in renal development and disease is still unclear. We show that Snail genes are downregulated during the MET that occurs during renal development and that this is correlated with Cadherin-16 expression. Snail suppresses Cadherin-16 via the direct repression of the kidney differentiation factor HNF-1beta, a novel route by which Snail disrupts epithelial homeostasis. Indeed, Snail activation is sufficient to induce EMT and kidney fibrosis in adult transgenic mice. Significantly, Snail is also activated in patients with renal fibrosis. Thus, Snail expression is suppressed during renal development and it must remain silent in the mature kidney where its aberrant activation leads to fibrosis.
Description:11 páginas, 7 figuras.
Publisher version (URL):http://dx.doi.org/10.1038/sj.emboj.7601421
URI:http://hdl.handle.net/10261/32371
ISSN:0261-4189
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Appears in Collections:(IN) Artículos

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