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

Fibroblast proliferation and extracellular matrix 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 paraquant 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 normal lungs, scattered macrophages contained FGF-1. In contrast, 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 and was virtually immonolocalized 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.