Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and lethal lung disease of unknown etiology. IPF begins in the subpleural region and extends centrally. Pleural mesothelial cells may contribute to pleural fibrosis. Key developmental lung signalling pathways such as FGFs are reactivated in IPF. During lung development, FGF9 is expressed in mesothelium and is implicated in the control of epithelial branching and mesenchymal proliferation. We observed that FGF9 is reactivated in pleural cells in IPF patients compared to controls. In this study, we investigated the effects of FGF9 on rat mesothelial cells proliferation, differentiation, and migration in vitro.
In basal condition, mesothelial cells mostly expressed receptors with a high affinity for FGF9 (FGFR3IIIc>FGFR2IIIc>FGFR1IIIc). TGFβ1 (5ng/ml) decreased the expression of FGFR3IIIc while FGFR4 expression was increased. In basal condition, FGF9 (20ng/ml) activated p-Erk, did not influence mesothelial cell proliferation, decreased Collagen-1 production, decreased α-smooth muscle actin (α-SMA) and Wilms tumor (WT1) expression and decreased mesothelial cells migratory abilities. FGF9 also partially prevented TGFβ1-induced mesothelial cell differentiation (collagen-1 expression) and migration upregulation.
These results suggest that FGF9 modulates mesothelial cells plasticity to maintain an undifferentiated and anti-migratory phenotype and could have an antifibrogenic role in the early phase of IPF.
- Copyright ©the authors 2016
