The expression profile of Claudin family members in the developing mouse lung and expression alterations resulting from exposure to secondhand smoke (SHS)
The expression profile of Claudin family members in the developing mouse lung and expression alterations resulting from exposure to secondhand smoke (SHS)
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DOI：
10.1080/01902148.2017.1409846
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发表时间：
2018-01-01
影响因子：
1.7
通讯作者：
Reynolds, Paul R.
中科院分区：
文献类型：
--
作者：
Lewis, Joshua B.;Jimenez, Felix R.;Reynolds, Paul R.
紧密连接蛋白是紧密连接蛋白，参与细胞极性和上皮屏障的维持。紧密连接蛋白的错误调节对细胞分化和增殖的发育方面产生不利影响。目前的研究评估了Claudins 1-11和18在胚胎（E）14.5、16.5和18.5天以及出生后（PN）3和PN 15天的发育小鼠肺中的转录表达。还通过免疫组织化学分析评估小鼠肺以定性评估Claudin蛋白表达。妊娠母鼠从胚胎日（E）15.5至18.5进一步暴露于二手烟（SHS），并立即在幼鼠肺中筛选Claudin mRNA。除了Claudin-6，Claudin家族成员的mRNA表达模式倾向于在E16.5降低，在E18.5增加，并且在PN 3再次降低，然后在PN 15达到表达峰值。Claudin-6 mRNA的表达下降，通过妊娠期和出生后的时期。免疫组织化学分析表明，Claudins的一个子集是近端与远端肺屏障建立的合理协调。在SHS暴露后E18.5时对紧密连接蛋白mRNA表达的评估显示，除了紧密连接蛋白-18（无变化）之外，所有紧密连接蛋白的转录均显著降低。这些数据支持需要使用基因靶向小鼠进行进一步研究，敲入/敲除特定的Claudin，以便确定正常和患病肺部的精确功能。
Claudins are tight junctional proteins implicated in cell polarity and epithelial barrier maintenance. Claudin misregulation adversely impacts developmental aspects of cell differentiation and proliferation. The current research evaluated transcriptional expression for Claudins 1-11 and 18 in the developing murine lung at embryonic days (E) 14.5, 16.5, and 18.5 and at post-natal day (PN) 3 and PN15. Mouse lungs were also assessed by immunohistochemical analysis to qualitatively evaluate Claudin protein expression. Pregnant dams were further exposed to secondhand smoke (SHS) from embryonic day (E)15.5 to 18.5 and Claudin mRNA was immediately screened in pup lungs. Other than Claudin-6, mRNA expression patterns for Claudin family members tended to decrease at E16.5, increase at E18.5, and decrease again at PN3 before reaching a peak of expression at PN15. Claudin-6 mRNA expression decreased through gestation and into post-natal periods. Immunohistochemical profiling implicated a subset of Claudins as plausible orchestrators of proximal vs. distal lung barrier establishment. Assessment of Claudin mRNA expression at E18.5 following SHS exposure revealed a significant reduction in transcription for all Claudins except Claudin-18 (no change). These data support the need for further studies using gene targeted mice that knock-in/out specific Claudins so that precise functions in the normal and diseased lung can be determined.