A nuclear receptor atlas: 3T3-L1 adipogenesis
A nuclear receptor atlas: 3T3-L1 adipogenesis
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DOI：
10.1210/me.2004-0539
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发表时间：
2005-10-01
影响因子：
--
通讯作者：
Mangelsdorf, DJ
中科院分区：
文献类型：
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作者：
Fu, MG;Sun, TW;Mangelsdorf, DJ
前脂肪细胞向成熟脂肪细胞的分化代表了生物学中的基本过程，其需要导致基因表达变化的转录事件的脚本程序。作为我们对核受体信号传导图谱（Nuclear Receptor Signaling Atlas，CRISSA）的贡献的一部分，我们使用两种分化诱导剂在3 T3-L1细胞分化为成熟的含脂脂肪细胞的过程中，在选定的时间点，使用定量实时PCR分析小鼠核受体超家族的所有49个成员的时间表达[2013年12月]。（地塞米松、3-异丁基-1-甲基黄嘌呤和胰岛素的混合物）和罗格列酮]。我们还对小鼠原代前脂肪细胞和成熟脂肪细胞的核受体表达进行了比较分析。除了确认已知脂肪形成所需的受体的表达外，该分析还揭示了在三个不同的时间阶段出现的严格调节的转录级联的存在。第一阶段开始在4小时内的脂肪形成开始与短暂的，连续表达的四个以前未表征的受体，其次是双相表达的第二个子集，并结束了连续增加的第三个受体子集在一段时间内的2周后开始。这些受体可用作脂肪形成生物标志物和脂肪相关疾病中的潜在治疗靶标的发现突出了定量表达谱作为指导基于机制的方法来研究复杂调控途径的方法的效用。
The differentiation of a preadipocyte into a mature adipocyte represents a fundamental process in biology that requires a scripted program of transcriptional events leading to changes in gene expression. As part of our contribution to the Nuclear Receptor Signaling Atlas (NURSA), we used quantitative real-time PCR to profile the temporal expression of all 49 members of the mouse nuclear receptor superfamily at selected time points during differentiation of 3T3-L1 cells into mature, lipid-bearing adipocytes using two differentiation inducers [DMI ( a cocktail of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin) and rosiglitazone]. We also included a comparative analysis of nuclear receptor expression in mouse primary preadipocytes and mature adipocytes. In addition to confirming the expression of receptors known to be required for adipogenesis, this analysis revealed the existence of a tightly regulated transcriptional cascade that appeared in three distinct temporal phases. The first phase began within 4 h of adipogenic initiation with the transient, sequential expression of four previously uncharacterized receptors, followed by biphasic expression of a second subset, and ended with the sequential increase in a third receptor subset over a period of 2 wk after initiation. The discovery that these receptors may serve as adipogenic biomarkers and as potential therapeutic targets in adipose- related diseases highlights the utility of quantitative expression profiling as a method for directing mechanism-based approaches to study complex regulatory pathways.