Upregulation of acidic fibroblast growth factor during development of experimental lung fibrosis

Fibroblast proliferation and extracellular matrix accumulation are crucial in the pathogenesis of lung fibrosis. Fibroblast growth factor (FGF)-1 participates in both processes, but its role in lung fibrogenesis has not been evaluated. We analyzed the expression of FGF-1 and of FGF receptor (FGFR) in a model of lung fibrosis induced in rats with paraquat plus hyperoxia. Experimental and control animals were killed at 48 h and 2, 4, and 8 wk, and the lungs were studied by in situ hybridization, immunohistochemistry, and Northern blot. In normal lungs, scattered macrophages contained FGF-1. In contrast, at all times examined, the injured lungs exhibited FGF-1 transcript and the immunoreactive protein, mainly in alveolar epithelial cells and macrophages. In advanced fibrotic lesions, fibroblasts also appeared stained. Northern blot corroborated the upregulation of FGF-1 mRNA. FGFR was not observed in normal lungs, whereas it was strongly increased in the damaged lungs and was virtually immunolocalized in the same cell types as the corresponding ligand. These findings suggest that FGF-1 and FGFR are actively synthesized during the development of pulmonary fibrosis.