Transforming growth factor-β1 modifies fibroblast growth factor-2 production in type II cells

Transforming growth factor (TGF)-beta (1) is an inflammatory cytokine that plays multiple roles in pulmonary fibrosis, In vascular epithelium, it has been shown to regulate production and activity of fibroblast growth factor (FGF)-2, a potent type II cell mitogen in the lung. Such a relationship could have important consequences in prefibrotic change in the lung alveolus, where reepithelialization of alveolar surfaces is crucial. The goal of this study was to determine if FGF-2 production by alveolar type II cells is modulated by TGF-beta, or FGF-1, another type II tell mitogen, Isolated rat type II cells were exposed to 0 to 40 ng/mL of TGF-beta (1) or 0 to 500 ng/mL of FGF-1 in serum-free medium for 1 to 3 days. Using a specific irnmunoassay significant increases in FGF-beta protein in type II cell lysates were achieved after 1 day of exposure to 100 ng/mL of FGF-1 and after 3 days of treatment with 8 ng/mL of TGF-beta (1), Similarly, transcripts for FGF-2 were dramatically increased with TGF-beta (1) or FGF-1, as were those for FGF receptor (FGFR)-1, These interactions were dramatically effected by the addition of heparin, a model sulfated extracellular matrix: (ECM). Heparin as low as 0.01 mg/mL significantly downregulated expression of TGF-beta (1) and FGF-1-stimulated FGF-2 and FGFR-1, These results demonstrate important regulatory links between FGF-2, sulfated ECMs, and both TGF-beta (1) and FGF-1, which could contribute to the modulation of normal cell turnover, development, and repair processes attendant to fibrosis in the lung.