Transforming growth factor-beta(1) 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(1) or FGF-1, another type II cell 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 immunoassay, significant increases in FGF-2 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.
Li
C M
CM
Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, Raleigh, NC 27606, USA.
Khosla
J
J
Hoyle
P
P
Sannes
P L
PL
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2