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Proliferation Genes Repressed by TGF-β Are Downstream of Slug/Snail2 in Normal Bronchial Epithelial Progenitors and Are Deregulated in COPD

Abstract : Slug/Snail2 belongs to the Epithelial-Mesenchymal Transition (EMT)-inducing transcription factors involved in development and diseases. Slug is expressed in adult stem/progenitor cells of several epithelia, making it unique among these transcription factors. To investigate Slug role in human bronchial epithelium progenitors, we studied primary bronchial basal/progenitor cells in an air-liquid interface culture system that allows regenerating a bronchial epithelium. To identify Slug downstream genes we knocked down Slug in basal/progenitor cells from normal subjects and subjects with COPD, a respiratory disease presenting anomalies in the bronchial epithelium and high levels of TGF-β in the lungs. We show that normal and COPD bronchial basal/progenitors, even when treated with TGF-β, express both epithelial and mesenchymal markers, and that the epithelial marker E-cadherin is not a target of Slug and, moreover, positively correlates with Slug. We reveal that Slug downstream genes responding to both differentiation and TGF-β are different in normal and COPD progenitors, with in particular a set of proliferation-related genes that are among the genes repressed downstream of Slug in normal but not COPD. In COPD progenitors at the onset of differentiation in presence of TGF-β, we show that there is positive correlations between the effect of differentiation and TGF-β on proliferation-related genes and on Slug protein, and that their expression levels are higher than in normal cells. As well, the expression of Smad3 and β-Catenin, two molecules from TGF-β signaling pathways, are higher in COPD progenitors, and our results indicate that proliferation-related genes and Slug protein are increased by different TGF-β-induced mechanisms.
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https://hal-cnrs.archives-ouvertes.fr/hal-03427250
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Submitted on : Saturday, November 13, 2021 - 11:23:27 AM
Last modification on : Tuesday, January 4, 2022 - 5:59:34 AM

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  • HAL Id : hal-03427250, version 1

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Chamseddine Ben Brahim, Charlotte Courageux, Ariane Jolly, Bérengère Ouine, Aurélie Cartier, et al.. Proliferation Genes Repressed by TGF-β Are Downstream of Slug/Snail2 in Normal Bronchial Epithelial Progenitors and Are Deregulated in COPD. Stem Cell Reviews and Reports, Humana Press, 2021. ⟨hal-03427250⟩

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