TY - JOUR T1 - LSC Abstract – Activation of FGF9 and 18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4031 VL - 48 IS - suppl 60 SP - PA4031 AU - Audrey Joannes AU - Madeleine Jaillet AU - Arnaud Mailleux AU - Bruno Crestani Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4031.abstract N2 - Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in epithelial–mesenchymal interactions and are critical for lung development.We evaluated the expression of FGF9, FGF18 and FGFR in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration and differentiation of control and IPF human lung fibroblasts (HLF).HLF were cultured with FGF9 and FGF18. FAS-ligand induced apoptosis was assayed by measuring cleaved-PARP expression. Expression of FGFR mRNA, α-smooth muscle actin, collagen I and MMPs was analyzed with qPCR, western blot and zymography. Migratory capacities were evaluated in a modified Boyden chamber. siRNA were used to test FGFR3 implication.FGF9, FGF18 and all FGFR were present in the remodeled alveolar epithelium close to the fibroblast foci. Only FGFR3 was expressed in fibroblast foci. In vitro, FGF9 did not affect fibroblasts proliferation. FGF9/FGF18 decreased Fas-ligand induced apoptosis in control but not in IPF fibroblasts. FGF9 prevented basal and TGF-β1–induced myofibroblast differentiation. FGF9/FGF18 increased the migratory capacities of HLF, and FGF9 actively modulated MMPs activity. HLF mostly expressed FGFR1c and FGFR3b. FGFR3 inhibition prevented pERK activation by FGF9/FGF18 and partially inhibited their effect on differentiation and migration.These results identify FGF9 as an anti-apoptotic, anti-differentation and pro-migratory growth factor. FGF18 was a less potent molecule. FGFR3 drives part of the action of FGF9/FGF18. Both growth factors likely contribute to the fibrotic process.This abstract has been presented previously at the European Respiratory Society's Lung Science Conference in March 2016. ER -