Targeting HuR-Vav3 mRNA interaction prevents ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Targeting HuR-Vav3 mRNA interaction prevents Pseudomonas aeruginosa adhesion to the cystic fibrosis airway epithelium.
Author(s) :
Badaoui, Mehdi [Auteur]
Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 [LPCM]
Sobolewski, Cyril [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Luscher, Alexandre [Auteur]
Bacchetta, Marc [Auteur]
Köhler, Thilo [Auteur]
Van Delden, Christian [Auteur]
Hôpitaux universitaires de Genève = University Hospitals of Geneva [HUG]
Foti, Michelango [Auteur]
Chanson, Marc [Auteur]
Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 [LPCM]
Sobolewski, Cyril [Auteur]

Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Luscher, Alexandre [Auteur]
Bacchetta, Marc [Auteur]
Köhler, Thilo [Auteur]
Van Delden, Christian [Auteur]
Hôpitaux universitaires de Genève = University Hospitals of Geneva [HUG]
Foti, Michelango [Auteur]
Chanson, Marc [Auteur]
Journal title :
JCI Insight
Abbreviated title :
JCI Insight
Volume number :
8
Pages :
e161961
Publication date :
2023-01-08
ISSN :
2379-3708
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF ...
Show more >Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF airways. The guanine nucleotide exchange factor Vav3 plays a critical role in Pa adhesion to the CF airways by inducing luminal fibronectin deposition that favors bacteria trapping. Here we report that Vav3 overexpression in CF is caused by upregulation of the mRNA-stabilizing protein HuR. We found that HuR accumulates in the cytoplasm of CF airway epithelial cells and that it binds to and stabilizes Vav3 mRNA. Interestingly, disruption of the HuR-Vav3 mRNA interaction improved the CF epithelial integrity, inhibited the formation of the fibronectin-made bacterial docking platforms, and prevented Pa adhesion to the CF airway epithelium. These findings indicate that targeting HuR represents a promising antiadhesive approach in CF that can prevent initial stages of Pa infection in a context of emergence of multidrug-resistant pathogens.Show less >
Show more >Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF airways. The guanine nucleotide exchange factor Vav3 plays a critical role in Pa adhesion to the CF airways by inducing luminal fibronectin deposition that favors bacteria trapping. Here we report that Vav3 overexpression in CF is caused by upregulation of the mRNA-stabilizing protein HuR. We found that HuR accumulates in the cytoplasm of CF airway epithelial cells and that it binds to and stabilizes Vav3 mRNA. Interestingly, disruption of the HuR-Vav3 mRNA interaction improved the CF epithelial integrity, inhibited the formation of the fibronectin-made bacterial docking platforms, and prevented Pa adhesion to the CF airway epithelium. These findings indicate that targeting HuR represents a promising antiadhesive approach in CF that can prevent initial stages of Pa infection in a context of emergence of multidrug-resistant pathogens.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-11T23:45:47Z
2024-01-26T10:10:53Z
2024-01-26T10:10:53Z
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