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Yasuji Ueda, Coral G. Chamberlain, Kenshi Satoh, John W. McAvoy; Inhibition of FGF-Induced αA-Crystallin Promoter Activity in Lens Epithelial Explants by TGFβ. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1833-1839.
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purpose. Fibroblast growth factor (FGF) plays a key role in normal lens biology,
and recent studies suggest that transforming growth factor (TGF)-β is
involved in the origin of certain forms of cataract. In the current
study, the effects of FGF and TGFβ on αA-crystallin promoter
activity were investigated.
methods. Rat lens epithelial explants were cultured with or without growth
factors after transfecting with the firefly luciferase reporter gene
driven by either the mouse αA-crystallin promoter region or a control
simian virus (SV)40 promoter.
results. FGF-2, at a concentration that induced lens fiber differentiation,
strongly stimulated αA-crystallin promoter activity in explants at 3
to 4 days of culture, whereas SV40 promoter control specimens showed no
comparable increase. At lower concentrations of FGF, sufficient to
induce cell proliferation but not differentiation, there was only a
slight increase in αA-crystallin promoter activity. Stimulation ofα
A-crystallin promoter activity induced by the fiber-differentiating
concentration of FGF was virtually abolished by as little as 25 pg/ml
TGFβ2, but the onset of fiber-specific β-crystallin accumulation
was not prevented at this concentration. Phase-contrast microscopy
revealed overt cataractous changes only at concentrations of TGFβ
more than 25 pg/ml.
conclusions. The stimulation of αA-crystallin promoter activity by FGF is
consistent with its role in inducing accumulation of crystallins in
explants. The blocking effect of TGFβ on this process, even at a
concentration too low to induce obvious pathologic changes, indicates
the potential for TGFβ to disturb αA-crystallin gene expression
during early fiber differentiation.
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