Maternal smoking and the retinoid pathway in the developing lung.
Maternal smoking and the retinoid pathway in the developing lung.
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DOI：
10.1186/1465-9921-13-42
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Haley KJ
中科院分区：
文献类型：
--
作者：
Manoli SE;Smith LA;Vyhlidal CA;An CH;Porrata Y;Cardoso WV;Baron RM;Haley KJ
母亲吸烟是儿童肺部疾病的一个危险因素，包括哮喘。动物模型表明，母亲吸烟会导致后代肺泡发育缺陷。视黄酸信号调节肺发育和出生后免疫功能。因此，这一通路的异常可能介导母体吸烟的影响。我们在小鼠模型中测试了母亲吸烟是否会破坏维甲酸途径的表达和功能。雌性C57Bl/6小鼠暴露于/不暴露于主流香烟烟雾（每天3支研究用香烟，每周5天），与不吸烟的雄性交配。在整个怀孕期间和分娩后，吸烟持续存在。采用平均线性截距分析和定量PCR检测子代肺组织。采用II型细胞样细胞系A549进行细胞培养实验，检测了脂溶性香烟烟雾成分是否影响体外维甲酸反应元件的结合和激活。与tobacco-naïve小鼠相比，烟草毒素暴露的幼鼠平均线性截距显著（P < 0.05）增加，与肺泡缺损一致。烟草毒素暴露显著（P < 0.05）降低了视黄酸信号通路元件（视黄酸受体α和视黄酸受体β） mRNA和蛋白的表达，且以出生后3 ~ 5 d变化最多。脂溶性香烟烟雾成分显著（P < 0.05）降低了维甲酸诱导的A549细胞维甲酸受体反应元件的结合和激活。一个小鼠模型的母亲吸烟引起异常肺泡化与改变维甲酸途径元件表达在后代。体外细胞培养模型表明，香烟烟雾的脂溶性成分会降低维甲酸反应元件的激活。视黄酸信号的破坏可能与母亲吸烟引起的儿童肺功能障碍有关。
Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model. Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week) were mated to nonsmoking males. Cigarette smoke exposure continued throughout the pregnancy and after parturition. Lung tissue from the offspring was examined by mean linear intercept analysis and by quantitative PCR. Cell culture experiments using the type II cell-like cell line, A549, tested whether lipid-soluble cigarette smoke components affected binding and activation of retinoic acid response elements in vitro. Compared to tobacco-naïve mice, juvenile mice with tobacco toxin exposure had significantly (P < 0.05) increased mean linear intercepts, consistent with an alveolarization defect. Tobacco toxin exposure significantly (P < 0.05) decreased mRNA and protein expression of retinoic acid signaling pathway elements, including retinoic acid receptor alpha and retinoic acid receptor beta, with the greatest number of changes observed between postnatal days 3–5. Lipid-soluble cigarette smoke components significantly (P < 0.05) decreased retinoic acid-induced binding and activation of the retinoic acid receptor response element in A549 cells. A murine model of maternal cigarette smoking causes abnormal alveolarization in association with altered retinoic acid pathway element expression in the offspring. An in vitro cell culture model shows that lipid-soluble components of cigarette smoke decrease retinoic acid response element activation. It is feasible that disruption of retinoic acid signaling contributes to the pediatric lung dysfunction caused by maternal smoking.
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影响因子：
6.4
作者：
Chen, GQ;Lin, BZ;Zhang, XK
通讯作者：
Zhang, XK
影响因子：
4.8
作者：
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通讯作者：
Chytil, F
DOI：
10.1152/ajplung.00534.2007
发表时间：
2008-07-01
影响因子：
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作者：
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作者：
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通讯作者：
Cardoso, WV
影响因子：
3.1
作者：
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