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FGF9 prevents pleural fibrosis induced by intra-pleural adenovirus injection in mice

Abstract : Fibroblast growth factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (AdCont) was performed. Mice were euthanized at days 3, 5, and 14 Expression of FGF9 and markers of inflammation and myofibroblastic differentiation was studied by qPCR and immunohistochemistry. In vitro, rat mesothelial cells were stimulated with FGF9 (20 ng/ml), and we assessed its effect on proliferation, survival, migration, and differentiation. FGF9 was expressed by mesothelial cells in human idiopathic pulmonary fibrosis. FGF receptors, mainly FGFR3, were expressed by mesothelial cells in vivo in humans and mice. AdCont instillation induced diffuse pleural thickening appearing at day 5, maximal at day 14 The altered pleura cells strongly expressed α-smooth muscle actin and collagen. AdFGF9 injection induced maximal FGF9 expression at day 5 that lasted until day 14 FGF9 overexpression prevented pleural thickening, collagen and fibronectin accumulation, and myofibroblastic differentiation of mesothelial cells. In vitro, FGF9 decreased mesothelial cell migration and inhibited the differentiating effect of transforming growth factor-β1. We conclude that FGF9 has a potential antifibrotic effect on mesothelial cells.
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Contributeur : LNC - université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mardi 12 décembre 2017 - 17:45:15
Dernière modification le : dimanche 26 juin 2022 - 01:54:44

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Aurélie Justet, Audrey Joannes, Valerie Besnard, Joëlle Marchal-Sommé, Madeleine Jaillet, et al.. FGF9 prevents pleural fibrosis induced by intra-pleural adenovirus injection in mice. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017, 313 (5), pp.L781-L795. ⟨10.1152/ajplung.00508.2016⟩. ⟨hal-01662162⟩



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