Co-alterations of circadian clock gene transcripts in human placenta in preeclampsia.
Co-alterations of circadian clock gene transcripts in human placenta in preeclampsia.
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DOI：
10.1038/s41598-022-22507-3
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发表时间：
2022-10-25
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先兆子痫 (PE) 是一种妊娠期间发生的高血压疾病，导致高达 4% 的妊娠并发症。 PE 表现出多种与昼夜节律相关的特征，并且胎盘具有功能性分子钟。我们使用两个独立的基因表达数据集：GSE75010-157（80 个 PE 与 77 个非 PE）和 GSE75010-173（77 个 PE 和 96 个非 PE）检查了胎盘中 17 个核心昼夜节律基因转录本与 PE 与非 PE（足月、早产、小于胎龄或绒毛膜羊膜炎的孕妇的混合物）之间的关联。我们发现两个数据集中 PE 和非 PE 之间的昼夜节律基因表达存在显着差异，其中 PE 胎盘中 CRY1 mRNA 增加，NR1D2 和 PER3 转录物减少。基因组变异分析揭示了生物钟基因和 PE 的共同改变与缺氧、细胞迁移/入侵、自噬和膜运输途径改变之间的相互作用。使用人胎盘滋养层 HTR-8 细胞，我们发现 CRY1/2 和 NR1D1/2 调节滋养层迁移。一项仅包括足月样本的亚组研究表明，PE 胎盘中 CLOCK、NR1D2 和 PER3 转录本同时减少，这一发现得到人类足月 PE 胎盘样本独立队列中 CLOCK 蛋白下调的支持。这些发现为分子钟在 PE 发病机制中的作用提供了新的见解。
Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs. non-PE (a mixture of pregnant women with term, preterm, small-for-gestational-age, or chorioamnionitis) using two independent gene expression datasets: GSE75010-157 (80 PE vs. 77 non-PE) and GSE75010-173 (77 PE and 96 non-PE). We found a robust difference in circadian gene expression between PE and non-PE across the two datasets, where CRY1 mRNA increases and NR1D2 and PER3 transcripts decrease in PE placenta. Gene set variation analysis revealed an interplay between co-alterations of circadian clock genes and PE with altered hypoxia, cell migration/invasion, autophagy, and membrane trafficking pathways. Using human placental trophoblast HTR-8 cells, we show that CRY1/2 and NR1D1/2 regulate trophoblast migration. A subgroup study including only term samples demonstrated that CLOCK, NR1D2, and PER3 transcripts were simultaneously decreased in PE placenta, a finding supported by CLOCK protein downregulation in an independent cohort of human term PE placenta samples. These findings provide novel insights into the roles of the molecular clock in the pathogenesis of PE.
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影响因子：
2.2
作者：
Akiyama, Shizuko;Ohta, Hidenobu;Yaegashi, Nobuo
通讯作者：
Yaegashi, Nobuo
DOI：
10.1136/bmj.f6564
发表时间：
2013-11-07
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Ananth CV;Keyes KM;Wapner RJ
通讯作者：
Wapner RJ
影响因子：
3
作者：
Bouchlariotou, Sofia;Liakopoulos, Vassilios;Stefanidis, Ioannis
通讯作者：
Stefanidis, Ioannis
影响因子：
3.4
作者：
Iacobelli, Silvia;Bonsante, Francesco;Robillard, Pierre-Yves
通讯作者：
Robillard, Pierre-Yves
DOI：
10.1016/j.bbrc.2008.11.006
发表时间：
2009-01-02
影响因子：
3.1
作者：
Frigato, Elena;Lunghi, Laura;Bertolucci, Cristiano
通讯作者：
Bertolucci, Cristiano