FGF19 is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits Lung Fibrosis in Mice.
Fiche publication
Date publication
mai 2022
Journal
American journal of respiratory cell and molecular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BONNIAUD Philippe
Tous les auteurs :
Justet A, Ghanem M, Boghanim T, Hachem M, Vasarmidi E, Jaillet M, Vadel A, Joannes A, Mordant P, Bonniaud P, Kolb M, Ling L, Cazes A, Mal H, Mailleux A, Crestani B
Lien Pubmed
Résumé
IPF is a devastating lung disease with limited therapeutic possibilities. FGF19, an endocrine FGF, was recently shown to decrease liver fibrosis. To ask whether FGF19 had anti-fibrotic properties in the lung and decipher its effects on common features associated with lung fibrogenesis. We assessed, by Elisa, FGF19 levels in plasma and bronchoalveolar lavage fluids (BALF)obtained from controls and IPF patients. In vivo, using an intravenously administered adeno11 associated virus (AAV), we overexpressed FGF19 at the fibrotic phase of two experimental models of murine lung fibrosis and assessed its effect on lung morphology, lung collagen content, fibrosis markers and pro fibrotic mediator expression, at mRNA and protein levels. In vitro, we investigated whether FGF19 could modulate the TGFβ-induced differentiation of primary human lung fibroblast into myofibroblast and the apoptosis of murine alveolar type II cell. While FGF19 was not detected in BALF, FGF19 concentration was decreased in the plasma of IPF patients compared to controls. In vivo, the overexpression of FGF19 was associated with a marked decrease of lung fibrosis and fibrosis markers, with a decrease of pro fibrotic mediator expression and lung collagen content. In vitro, FGF19 decreased alveolar type 2 epithelial cell apoptosis through the decrease of the proapoptotic BIM protein expression and prevented TGF-ß induced myofibroblast differentiation through the inhibition of JNK phosphorylation. Altogether these data identify FGF19 as an anti-fibrotic molecule with a potential therapeutic interest in fibrotic lung disorders.
Référence
Am J Respir Cell Mol Biol. 2022 05 12;: