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Caractérisation de la voie Hedgehog dans la différenciation de l'épithélium des voies aériennes et altération dans la BPCO

Abstract : Hedgehog (HH) pathway is crucial for organogenesis and homeostasis. Since HH signaling is involved in pulmonary quiescence and repair, and altered in chronic lung diseases, we investigated HH signalling during airway epithelial cell differentiation and its incidence on Chronic Obstructive Pulmonary Disease (COPD)-associated remodeling. In vitro we demonstrated a correlation between HH pathway actors expression and differentiation. We identified basal cells as the source of the main pathway ligand, Sonic Hedgehog (Shh). Preventing the ligand-induced HH activation led to the establishment of a remodeled epithelium with reduced cilliogenesis. We also observed HH signalling alteration in COPD patient, especially a loss of Gli2 transcription factor expression and localization. Finally, we revealed the possibility to evaluate HH expression in clinical routine. Our collected data confirm HH pathway alteration in COPD patients in correlation with Gli2 transcriptomic and proteomic expression associated with a decrease of Shh ligand secretion. This study highlights the importance of the HH pathway in airway epithelial cell differentiation and identifies for the first time an alteration of this pathway in COPD patient. Understanding the molecular mechanisms associated with HH pathway in pathogenesis would open the way to new therapeutic strategies in this disease without available treatments.
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https://hal.univ-reims.fr/tel-03155908
Contributor : Valerian Dormoy <>
Submitted on : Tuesday, March 2, 2021 - 10:27:59 AM
Last modification on : Monday, May 17, 2021 - 2:52:24 PM
Long-term archiving on: : Monday, May 31, 2021 - 6:27:53 PM

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Randa Belgacemi. Caractérisation de la voie Hedgehog dans la différenciation de l'épithélium des voies aériennes et altération dans la BPCO. Organisation et fonctions cellulaires [q-bio.SC]. Université de Reims Champagne-Ardenne, 2020. Français. ⟨tel-03155908⟩

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