
The study investigated the role of fibroblast growth factor receptor-4 (FGFR4) in idiopathic pulmonary fibrosis (IPF), a severe lung disease with limited treatments. FGFR4 was found to be downregulated in IPF lungs compared to control lungs. In vitro, FGFR4 was downregulated by TGF-β, endothelin-1, and platelet-derived growth factor (PDGF). Inhibition of FGFR4 using the pharmacological inhibitor FGF401 or genetic deletion in murine embryonic fibroblasts (MEFs) prevented TGF-β-induced myofibroblast differentiation, suggesting that FGFR4 promotes fibrosis by enhancing TGF-β signaling. However, in vivo studies showed that FGFR4 genetic deficiency or inhibition did not prevent the development of bleomycin-induced lung fibrosis. These findings suggest that while FGFR4 has profibrotic properties in vitro, its inhibition is insufficient to block pulmonary fibrosis in vivo.
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