TY - JOUR T1 - Fibroblast growth factor 9 (FGF9) modulates the phenotype of control and fibrotic human lung fibroblasts<em> in vitro</em> JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3912 AU - Audrey Joannes AU - Joelle Marchal-Somme AU - Laura Giersch AU - Bruno Crestani AU - Arnaud Mailleux Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3912.abstract N2 - Introduction: Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix (ECM) proteins and fibroblasts in the distal airways. Key developmental lung signalling pathways are reactivated in IPF. During lung development, FGF9 is produced by epithelial cells and controls mesenchyme proliferation and patterning during branching morphogenesis. We investigated the effects of FGF9 on proliferation, myofibroblastic differentiation, survival and migration of control and IPF human lung fibroblasts in vitro.Methods: Control and IPF fibroblasts (N=6) were cultured with FGF9 (20ng/ml) (24 or 48 h).Growth rate was evaluated by cell count. FAS-ligand induced apoptosis was assayed by measuring caspase 3/7 activity.Expression of FGF receptors (FGFR) mRNA, and α-smooth muscle actin, collagen I and fibronectin was analyzed with qPCR and western blot. Migratory capacities were evaluated in a modified Boyden chamber.Results: Fgfr1IIIc, Fgfr3IIIc and Fgfr4 are the main FGFR expressed in control and IPF fibroblasts. FGF9 did not influence fibroblast proliferation or differentiation of control and IPF fibroblasts in presence or absence of TGF-b1 (1ng/ml). FGF9 decreased caspase 3/7 activity induced by Fas-ligand activation in control fibroblast (-25%) but not in IPF fibroblast. FGF9 increased the migratory capacity of control (4.1 fold) and IPF (3.5 fold) fibroblasts.Conclusion: These results identify FGF9 as a potential pro-survival and pro-migratory growth factor on lung fibroblast that could contribute to lung fibrosis.This work was supported by the Agence Nationale pour la Recherche (ANR-11-BSV1-0011), Boehringer Ingelheim and the LabEx Inflamex. ER -