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 cou
ld 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 mo
dulated by TGF-beta, or FGF-1, another type II tell mitogen, Isolated rat t
ype II cells were exposed to 0 to 40 ng/mL of TGF-beta (1) or 0 to 500 ng/m
L of FGF-1 in serum-free medium for 1 to 3 days. Using a specific irnmunoas
say 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 we
re dramatically increased with TGF-beta (1) or FGF-1, as were those for FGF
receptor (FGFR)-1, These interactions were dramatically effected by the ad
dition of heparin, a model sulfated extracellular matrix: (ECM). Heparin as
low as 0.01 mg/mL significantly downregulated expression of TGF-beta (1) a
nd FGF-1-stimulated FGF-2 and FGFR-1, These results demonstrate important r
egulatory links between FGF-2, sulfated ECMs, and both TGF-beta (1) and FGF
-1, which could contribute to the modulation of normal cell turnover, devel
opment, and repair processes attendant to fibrosis in the lung.