FGF19, a potential innovative target in Idiopathic Pulmonary Fibrosis?

Introduction: IPF is characterized by a reactivation of signaling pathways involved in lung development, such as Fibroblast Growth Factors (FGF). FGFR4 is a FGF receptor activated by endocrine FGF like FGF19. FGFR4 is expressed in the normal and fibrotic lung. Recent evidence indicates that overexpression of FGF19 have antifibrotic properties in experimental liver fibrosis. The aim of this study was to determine the lung anti fibrotic properties of FGF19 in vitro and in vivo Material and Methods: We assessed FGF19 in plasma by Elisa from controls and IPF patients. Human lung fibroblasts from IPF and control patients were stimulated by TGF s (1ng/mL) with or without FGF19 (20 ng/mL) during 30 minutes or 48 hours. Adeno-associated virus-FGF19 (AAV-FGF19) or a control (AAV-GFP) (6x1010 viral genomes) was IV administered in C56/Bl6 male mice at day 0. Intratracheal administration of bleomycine was realized at day 14. ELISA studied mice at day 28. We quantified plasma FGF-19 levels. We assessed inflammation and pro fibrotic markers by qPCR, and western blot. Results: Compared to controls, FGF19 level plasma was significantly decreased in plasma from IPF patients. In vitro, FGF19 prevented the TGFs induced myofibroblast differentiation by decreasing αSMA, Collagen1, fibronectin expression (mRNA and protein levels.) and JNK phosphorylation. In vivo, the AAV-FGF19 group showed significantly less lung fibrosis and a decrease of fibrosis marker at mRNA and protein levels 14 days after bleomycine exposure. Conclusion and Perspective: FGF19 have anti-fibrotic properties in the lung and could be an innovative therapeutic target in IPF. Further studies are needed to determine the implication of FGFR4 in FGF19 anti fibrotic properties.