A molecular clock regulates angiopoietin-like protein 2 expression.
A molecular clock regulates angiopoietin-like protein 2 expression.
复制标题
DOI：
10.1371/journal.pone.0057921
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Oike Y
中科院分区：
文献类型：
--
作者：
Kadomatsu T;Uragami S;Akashi M;Tsuchiya Y;Nakajima H;Nakashima Y;Endo M;Miyata K;Terada K;Todo T;Node K;Oike Y
各种生理和行为过程表现出昼夜节律性。这些节律通常由核心时钟基因的负反馈回路维持，即CLOCK、BMAL、PER和CRY。最近，生物钟功能障碍已被认为是生活方式相关疾病（如肥胖、心血管疾病和某些癌症）的病理生理学的重要基础。我们已经报道了血管生成素样蛋白2（ANGPTL 2）通过诱导慢性炎症而参与这些生活方式相关疾病的发病机制。然而，ANGPTL 2表达调控的分子机制知之甚少。在这里，我们评估了ANGPTL 2在各种小鼠组织中表达的昼夜节律性。我们观察到ANGPTL 2的节律性与PER 2基因的节律性相似，后者受CLOCK/BMAL 1复合物的调节。人ANGPTL 2基因的启动子活性被CLOCK和BMAL 1显著诱导，CRY共表达显著减弱了这种诱导。我们还鉴定了ANGPTL 2启动子中的功能性E盒，并观察了人骨肉瘤细胞中内源性CLOCK对这些位点的占据。此外，Cry缺陷小鼠表现出免疫性Angptl 2表达。总之，这些数据表明ANGPTL 2的周期性表达受分子钟调节。
Various physiological and behavioral processes exhibit circadian rhythmicity. These rhythms are usually maintained by negative feedback loops of core clock genes, namely, CLOCK, BMAL, PER, and CRY. Recently, dysfunction in the circadian clock has been recognized as an important foundation for the pathophysiology of lifestyle-related diseases, such as obesity, cardiovascular disease, and some cancers. We have reported that angiopoietin-like protein 2 (ANGPTL2) contributes to the pathogenesis of these lifestyle-related diseases by inducing chronic inflammation. However, molecular mechanisms underlying regulation of ANGPTL2 expression are poorly understood. Here, we assess circadian rhythmicity of ANGPTL2 expression in various mouse tissues. We observed that ANGPTL2 rhythmicity was similar to that of the PER2 gene, which is regulated by the CLOCK/BMAL1 complex. Promoter activity of the human ANGPTL2 gene was significantly induced by CLOCK and BMAL1, an induction markedly attenuated by CRY co-expression. We also identified functional E-boxes in the ANGPTL2 promoter and observed occupancy of these sites by endogenous CLOCK in human osteosarcoma cells. Furthermore, Cry-deficient mice exhibited arrhythmic Angptl2 expression. Taken together, these data suggest that periodic expression of ANGPTL2 is regulated by a molecular clock.
登录
查看更多内容
DOI：
10.1073/pnas.0808180106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Scheer, Frank A. J. L.;Hilton, Michael F.;Shea, Steven A.
通讯作者：
Shea, Steven A.
影响因子：
4.7
作者：
Shimizu, Fumiko;Fukada, Yoshitaka
通讯作者：
Fukada, Yoshitaka
影响因子：
4.8
作者：
Koyanagi, Satoru;Hamdan, Ahmed M.;Ohdo, Shigehiro
通讯作者：
Ohdo, Shigehiro
DOI：
10.1038/nrg2430
发表时间：
2008-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Paschos GK;FitzGerald GA
通讯作者：
FitzGerald GA