Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix proteins and fibroblasts in the distal airways. Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in critical epithelial-mesenchymal interactions during lung development. The recent Nintedanib approval for IPF also shed a new light on the potential role of the FGF signaling pathway in this deadly lung disease.
Our preliminary study in control and IPF lungs by immunohistochemistry showed that FGF9 and FGF18 were mainly detected in the hyperplastic epithelium. Therefore, we investigated the effects of FGF9 and FGF18 on proliferation, survival, myofibroblastic differentiation and migration of control and IPF primary human lung fibroblasts in vitro.
Our results show that FGF9 did not influence control or IPF fibroblasts proliferation whereas FGF18 inhibited cells growth in control fibroblasts only. In addition, only control lung fibroblasts were also protected by FGF9 and FGF18 from FAS-L induced apoptosis. In contrast, only FGF-9 partially prevented TGF-b1 induced myofibroblastic differentiation in control and IPF fibroblast as well. Finally, both FGF9 and FGF18 enhanced migratory capacities of control and IPF fibroblasts and upregulated MMPs expression.
These results identify both FGF9 and FGF-18 as potential anti-apoptotic and pro-migratory growth factors on lung fibroblasts and that could contribute to lung fibrosis. FGF9 and FGF18 also bear specific biological effects since they respectively negatively modulated myofibroblastic differentiation and proliferation.
- Copyright ©ERS 2015