Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray
Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray
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DOI：
10.1210/me.14.7.947
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发表时间：
2000-07-01
影响因子：
--
通讯作者：
Yen, PM
中科院分区：
文献类型：
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作者：
Feng, X;Jiang, Y;Yen, PM
肝脏是甲状腺激素的重要靶器官。然而，只有有限数量的肝脏靶基因已被确定，并很少有人知道他们的调控甲状腺激素的模式。我们使用定量荧光cDNA微阵列来鉴定甲状腺激素调控的新肝脏基因。将从T-3处理和甲状腺功能减退小鼠的肝脏RNA中制备的荧光标记的cDNA与代表2225种不同小鼠基因的cDNA微阵列杂交，然后进行计算机分析以比较基因表达的相对变化。55个基因，45个以前不知道是甲状腺激素反应基因，被发现受甲状腺激素调节。其中14个受甲状腺激素正调控，41个受甲状腺激素负调控。通过北方印迹分析证实了这些基因中的8个的表达。甲状腺激素影响多种细胞途径和功能的基因表达，包括胚胎发生、脂肪生成、胰岛素信号传导、腺苷酸环化酶信号传导、细胞增殖和凋亡。这是首次应用微阵列技术研究体内激素对基因表达的调节，并应被证明是未来激素和药物作用研究的有力工具。
The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T-3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression In vivo and should prove to be a powerful tool for future studies of hormone and drug action.