In vivo regulation of human skeletal muscle gene expression by thyroid hormone
In vivo regulation of human skeletal muscle gene expression by thyroid hormone
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DOI：
10.1101/gr.207702
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发表时间：
2002-02-01
期刊：
影响因子：
7
通讯作者：
Langin, D
中科院分区：
文献类型：
--
作者：
Clément, K;Viguerie, N;Langin, D
甲状腺激素是代谢的关键调节因子，通过核受体调节转录。甲状腺功能亢进症与代谢率增加、蛋白质分解和体重减轻有关。虽然甲状腺激素的分子作用已被彻底研究，但其多效性效应是由未知数量的靶基因表达的复杂变化介导的。在这里，我们使用24,000个cDNA元件微阵列测量了5名健康男性用75 μ g三碘甲腺原氨酸治疗14天后骨骼肌基因表达的模式。为了分析数据，我们使用了一种新的统计方法来识别表达的显著变化并估计错误发现率。这381个上调基因涉及广泛的细胞功能，包括转录控制、mRNA成熟、蛋白质周转、信号转导、细胞运输和能量代谢。只有两个基因被下调。大多数基因是甲状腺激素的新靶点。对19种不同的人体组织或细胞系中三碘甲状腺原氨酸调节基因表达的聚类分析揭示了具有相似生物学功能的共调节基因。这些结果定义了有助于理解甲状腺激素作用的生理学和病理生理学的分子特征。
Thyroid hormones are key regulators of metabolism that modulate transcription via nuclear receptors. Hyperthyroidism is associated with increased metabolic rate, protein breakdown, and weight loss. Although the molecular actions of thyroid hormones have been studied thoroughly, their pleiotropic effects are mediated by complex changes in expression of an unknown number of target genes. Here, we measured patterns of skeletal muscle gene expression in five healthy men treated for 14 days with 75 mug of triiodothyronine, using 24,000 cDNA element microarrays. To analyze the data, we used a new statistical method that identifies significant changes in expression and estimates the false discovery rate. The 381 up-regulated genes were involved in a wide range of cellular functions including transcriptional control, mRNA maturation, protein turnover, signal transduction, cellular trafficking, and energy metabolism. Only two genes were down-regulated. Most of the genes are novel targets of thyroid hormone. Cluster analysis of triiodothyronine-regulated gene expression among 19 different human tissues or cell lines revealed sets of coregulated genes that serve similar biologic functions. These results define molecular signatures that help to understand the physiology and pathophysiology of thyroid hormone action.