Glucocorticoid-induced changes in the global gene expression of lens epithelial cells
Glucocorticoid-induced changes in the global gene expression of lens epithelial cells
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DOI：
10.1089/jop.2005.21.11
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发表时间：
2005-02-01
影响因子：
2.3
通讯作者：
Robertson, LL
中科院分区：
文献类型：
--
作者：
James, ER;Fresco, VM;Robertson, LL
目的：临床上，类固醇的使用伴随着后囊膜下白内障（PSCs）的风险。PSC可能涉及晶状体上皮细胞增殖和分化的扰动；然而，其潜在机制尚不清楚。在这项研究中，我们旨在利用DNA微阵列杂交技术表征暴露于糖皮质激素的人晶状体上皮细胞基因表达的变化。方法：将人晶状体上皮细胞（HLE B-3）用地塞米松（I muM）或载药（0.01%二甲亚砜）处理24或48小时，并将衍生的cRNA与U133A微阵列杂交。使用Affymetrix程序Micro Array Suite处理数据，使用dChip软件进行本体论分析，过滤以排除上调或下调幅度小于2倍的转录本。结果：24小时时，57个转录本相对于对照上调2倍以上，50个转录本下调2倍以上。48小时时，92个转录本上调，42个转录本下调。在24小时和48小时数据集之间共享了22个上调转录本和2个下调转录本。主要的本体论分类是：信号转导、转录因子活性、细胞骨架/ECM/粘附、运输和细胞周期/发育。不同的本体论解释是可能的。结论：数据表明，晶状体上皮细胞的类固醇处理与几个功能类别的基因表达的显著变化有关，其中包括与细胞增殖相关的转录本。
Aims: Clinically, steroid use is accompanied by a risk for posterior subcapsular cataracts (PSCs). PSC possibly involves perturbation of lens epithelial cell proliferation and differentiation; however, the underlying mechanism is unknown. In this study, we aimed to characterize changes in gene expression in human lens epithelial cells exposed to glucocorticoid using DNA microarray hybridization.Methods: Human lens epithelial cells (HLE B-3) were treated with dexamethasone (I muM) for 24 or 48 hours or with vehicle (0.01% dimethylsulfoxide) and the derived cRNA was hybridized to U133A microarrays. Data were processed using the Affymetrix program Micro Array Suite, and ontological analyses were performed using the software dChip, filtering to exclude transcripts up- or down-regulated by less than 2-fold.Results: At 24 hours, 57 transcripts were upregulated relative to controls by greater than 2-fold and 50 were downregulated by greater than 2-fold. At 48 hours, 92 transcripts were upregulated and 42 were downregulated. Twenty-two upregulated and 2 downregulated transcripts were shared between the 24-hour and 48-hour data sets. The predominant ontological groupings were: signal transduction, transcription factor activity, cytoskeleton/ECM/adhesion, transport, and cell cycle/development. Alternate ontological interpretations are possible.Conclusions: The data indicate steroid treatment of lens epithelial cells is associated with significant changes in gene expression in several functional categories and these include transcripts related to cell proliferation.