13Nov 2024
FGFR4 Enhances Fibrosis, but Inhibition Fails to Block Pulmonary Fibrosis

FGFR4 Enhances Fibrosis, but Inhibition Fails to Block Pulmonary Fibrosis

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.

  • #pulmonology

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