Skip to Main content Skip to Navigation
Preprints, Working Papers, ...

Proliferation genes repressed by TGF-β are downstream of Slug/Snail2 in normal bronchial epithelial progenitors and are deregulated in COPD

Abstract : 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. Graphical Abstract
Document type :
Preprints, Working Papers, ...
Complete list of metadata

https://hal-cnrs.archives-ouvertes.fr/hal-03427280
Contributor : Pascale Leroy Connect in order to contact the contributor
Submitted on : Saturday, November 13, 2021 - 1:06:52 PM
Last modification on : Monday, November 15, 2021 - 3:09:05 AM

Links full text

Identifiers

Collections

Citation

Pascale Leroy. Proliferation genes repressed by TGF-β are downstream of Slug/Snail2 in normal bronchial epithelial progenitors and are deregulated in COPD. 2021. ⟨hal-03427280⟩

Share

Metrics

Record views

24