Insights into the role of EGFR in the modulation of fibronectin in the cystic fibrosis airway epitheluim

DirectorsChanson, Marcorcid
Imprimatur date2022-07-15
Defense date2022-07-15

Cystic Fibrosis (OMIM 219700) is an autosomal recessive disease due to mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The Cystic Fibrosis respiratory epithelium displays an aberrant expression of fibronectin with an ectopic apical localization. It creates a favorable environment for Pseudomonas aeruginosa attachment and proliferation leading to recurrent infections and inflammation. The expression of fibronectin is highly regulated by signaling pathways. In this work, we aim to understand whether the mutation in CFTR leads to a dysregulation in the epidermal growth factor receptor (EGFR) pathway and whether this pathway contributes to the ectopic expression of fibronectin in Cystic Fibrosis. On monolayers of airway epithelial cells, we show that EGFR signaling is not dysregulated. However, silencing EGFR or its downstream effector AKT leads to a downregulation of fibronectin only in CFTR knockdown (CFTR-KD) cells. In the CFTR-KD polarized epithelium, however EGFR is downregulated and mis-localized. Taken together, our data show there is a complex crosstalk between EGFR signaling and the expression of fibronectin in CFTR-KD monolayers. The role that EGFR and its effector play in a polarized epithelium is yet to be determined. The difference observed between monolayers and polarized cells accentuate the importance of choosing the most suitable cellular model that mimics the conditions in the human body.

Citation (ISO format)
BOU YOUNES, Marie-Therese A. Insights into the role of EGFR in the modulation of fibronectin in the cystic fibrosis airway epitheluim. 2022.
Main files (1)
Master thesis
  • PID : unige:163150

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Creation07/27/2022 10:21:00 AM
First validation07/27/2022 10:21:00 AM
Update time03/16/2023 7:28:36 AM
Status update03/16/2023 7:28:36 AM
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