Ueda Y, Chamberlain C G, Satoh K, McAvoy J W
Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, Australia.
Invest Ophthalmol Vis Sci. 2000 Jun;41(7):1833-9.
Fibroblast growth factor (FGF) plays a key role in normal lens biology, and recent studies suggest that transforming growth factor (TGF)-beta is involved in the origin of certain forms of cataract. In the current study, the effects of FGF and TGFbeta on alphaA-crystallin promoter activity were investigated.
Rat lens epithelial explants were cultured with or without growth factors after transfecting with the firefly luciferase reporter gene driven by either the mouse alphaA-crystallin promoter region or a control simian virus (SV)40 promoter.
FGF-2, at a concentration that induced lens fiber differentiation, strongly stimulated alphaA-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 alphaA-crystallin promoter activity. Stimulation of alphaA-crystallin promoter activity induced by the fiber-differentiating concentration of FGF was virtually abolished by as little as 25 pg/ml TGFbeta2, but the onset of fiber-specific beta-crystallin accumulation was not prevented at this concentration. Phase-contrast microscopy revealed overt cataractous changes only at concentrations of TGFbeta more than 25 pg/ml.
The stimulation of alphaA-crystallin promoter activity by FGF is consistent with its role in inducing accumulation of crystallins in explants. The blocking effect of TGFbeta on this process, even at a concentration too low to induce obvious pathologic changes, indicates the potential for TGFbeta to disturb alphaA-crystallin gene expression during early fiber differentiation.
成纤维细胞生长因子（FGF）在晶状体正常生物学过程中起关键作用，近期研究表明转化生长因子（TGF）-β参与某些形式白内障的发病机制。在本研究中，研究了FGF和TGF-β对αA-晶状体蛋白启动子活性的影响。
用小鼠αA-晶状体蛋白启动子区域或对照猿猴病毒（SV）40启动子驱动的萤火虫荧光素酶报告基因转染大鼠晶状体上皮外植体后，在有或无生长因子的情况下进行培养。
在诱导晶状体纤维分化的浓度下，FGF-2在培养3至4天时强烈刺激外植体中αA-晶状体蛋白启动子活性，而SV40启动子对照标本未见类似增加。在足以诱导细胞增殖但不诱导分化的较低FGF浓度下，αA-晶状体蛋白启动子活性仅略有增加。低至25 pg/ml的TGF-β2几乎完全消除了由纤维分化浓度的FGF诱导的αA-晶状体蛋白启动子活性刺激，但在此浓度下并未阻止纤维特异性β-晶状体蛋白积累的开始。相差显微镜检查仅在TGF-β浓度超过25 pg/ml时才显示明显的白内障样改变。
FGF对αA-晶状体蛋白启动子活性的刺激与其在诱导外植体中晶状体蛋白积累的作用一致。TGF-β对该过程的阻断作用，即使在浓度过低而无法诱导明显病理变化的情况下，也表明TGF-β在早期纤维分化过程中干扰αA-晶状体蛋白基因表达的可能性。
