Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately
Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately
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主流烟和侧流烟分别影响小鼠胚胎干细胞的心脏分化
DOI：
10.1016/j.tox.2016.05.017
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发表时间：
2016-05-16
期刊：
影响因子：
4.5
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Cheng, Wei;Zhou, Ren;Wang, Yan
流行病学研究表明，母亲吸烟和被动吸烟是导致后代先天性心脏病（CHD）发生的重要原因。卷烟烟气可分为主流烟气和侧流烟气，烟气化学研究表明，主流烟气和侧流烟气的组成存在显著差异。因此，怀疑MS和SS处理毒性的方式不同。然而，很少有人知道MS和SS诱导的发育效应的差异。在目前的研究中，心脏发育是通过小鼠胚胎干细胞（ESC）分化来模拟的。MS和SS暴露后，通过追踪骨形态发生蛋白（BMP）-Smad 4信号通路，观察到下游基因表达的中断，包括Gata 4，Mef 2c和Nkx2.5，以及肌球蛋白重链和肌球蛋白轻链。具体地，SS引起Gata 4表达的抑制，即使在非细胞毒性浓度下。此外，SS诱导的Gata 4启动子区域的低乙酰化反应了CS基因调节-表观遗传调控的协调。尽管SS诱导了ESC衍生的心肌细胞的凋亡，但Gata 4下调的细胞中的部分清除导致这些细胞存活并进行进一步分化，这为异常心脏发育奠定了潜在风险。初步揭示了MS和SS在心脏发育上的差异。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily. (C) 2016 Elsevier Ireland Ltd. All rights reserved.