Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.

Vanessa Louzier 1 William Raoul 1 Aude Leroux 2 Didier Branellec 2 Jean-Michel Caillaud 2 Hélène Many 1 Micheline Levame 1 Christophe Delclaux 1 Serge Adnot 1 Bernard Maitre 1, *
* Auteur correspondant
1 Physiopathologie et Thérapeutiques Respiratoires
2 Thérapie Génique et Cardiovasculaire
Abstract : High concentrations of oxygen can induce pulmonary toxicity and cause injury to alveolar epithelial and endothelial cells. The present study was performed to determine whether the potent epithelial and endothelial fibroblast growth factor 1 (FGF-1) protected against hyperoxia-induced lung injury. Recombinant adenovirus carrying the gene encoding human secreted FGF-1 (Ad. FGF1) increased the proliferation of lung epithelial cells in vitro. Ad.FGF1 or control vector with an empty expression cassette (Ad.V152) was administered intratracheally to Wistar rats. With Ad.FGF1 (10(9), 5 x 10(9), 10(10), or 5 x 10(10) viral particles [VP]), FGF-1 protein was found in bronchoalveolar lavage fluid 4 days postinfection at levels proportional to the viral dose and was detected in plasma after doses of 10(10) VP or more were administered. Histological examination of the lungs showed intense proliferation and apoptosis of alveolar and bronchial epithelial cells, with few inflammatory cells. The alveolar architecture returned to normal within 17 days. Rats pretreated with Ad.FGF1 (10(9) or 5 x 10(9) VP) 2 days before exposure to hyperoxia (95% O2) survived, whereas rats pretreated with Ad.V152 died within 3 days. In conclusion, adenovirus-mediated FGF-1 overexpression in the lungs causes epithelial cell proliferation and has beneficial effects in hyperoxic lung injury.
Type de document :
Article dans une revue
Human Gene Therapy, Mary Ann Liebert, 2004, 15 (8), pp.793-804. 〈10.1089/1043034041648390〉
Liste complète des métadonnées

Littérature citée [35 références]  Voir  Masquer  Télécharger
http://www.hal.inserm.fr/inserm-00990784
Contributeur : William Raoul <>
Soumis le : mercredi 14 mai 2014 - 10:26:02
Dernière modification le : mercredi 29 novembre 2017 - 10:29:38
Document(s) archivé(s) le : jeudi 14 août 2014 - 11:15:21

Fichier

2004_Hum_Gene_Ther.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Vanessa Louzier, William Raoul, Aude Leroux, Didier Branellec, Jean-Michel Caillaud, et al.. Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.. Human Gene Therapy, Mary Ann Liebert, 2004, 15 (8), pp.793-804. 〈10.1089/1043034041648390〉. 〈inserm-00990784〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

152

Téléchargements de fichiers

301

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD