Targeting HuR-Vav3 mRNA interaction prevents ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Targeting HuR-Vav3 mRNA interaction prevents Pseudomonas aeruginosa adhesion to the cystic fibrosis airway epithelium.
Auteur(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]
Titre de la revue :
JCI Insight
Nom court de la revue :
JCI Insight
Numéro :
8
Pagination :
e161961
Date de publication :
2023-01-08
ISSN :
2379-3708
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Date de dépôt :
2024-01-11T23:45:47Z
2024-01-26T10:10:53Z
2024-01-26T10:10:53Z
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