Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China; Center Laboratory of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Reprod Toxicol. 2017 Dec;74:10-22. doi: 10.1016/j.reprotox.2017.08.014. Epub 2017 Aug 24.
Long-term exposure to fine particulate matter (PM2.5) may cause adverse pregnancy outcomes but the mechanisms are not clear. Our research confirms that PM2.5 induced DNA damage, and inhibited cell proliferation in HTR-8/SVneo cells, presenting in a dose- and time-dependent manners. Using quantitative proteomics, the 182 and 486 differentially expressed proteins in cells treated with 120μgml PM2.5 for 24 and 48h were involved in many critical biological processes, including of cell proliferation, response to DNA damage, regulation of small GTPase mediated signal transduction, and etc. Further validation indicated that PM2.5 blocked the cell cycle at the G2/M phase through activation of the ATR-Cyclin E1/Cdk6 pathway, and it reduced the migration and invasion by upregulating TIMP1 and TIMP2 expression and downregulating Collagen I expression. Our findings were consistent with the observed effects of PM2.5 on cell cycle arrest and inhibition of migration and invasion in human extravillous trophoblast.
长期暴露于细颗粒物(PM2.5)可能导致不良的妊娠结局,但具体机制尚不清楚。我们的研究证实,PM2.5 可诱导 HTR-8/SVneo 细胞的 DNA 损伤,并呈剂量和时间依赖性抑制细胞增殖。通过定量蛋白质组学,研究发现暴露于 120μg/ml PM2.5 24 和 48 小时的细胞中,有 182 种和 486 种差异表达蛋白,这些蛋白参与了许多关键的生物学过程,包括细胞增殖、DNA 损伤反应、小 GTPase 介导的信号转导的调节等。进一步验证表明,PM2.5 通过激活 ATR-Cyclin E1/Cdk6 通路使细胞周期阻滞在 G2/M 期,并通过上调 TIMP1 和 TIMP2 的表达和下调 Collagen I 的表达,抑制细胞迁移和侵袭。我们的研究结果与 PM2.5 对人绒毛外滋养层细胞周期阻滞、迁移和侵袭抑制的观察结果一致。