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紧密连接蛋白家族成员在发育中的小鼠肺中的表达谱以及二手烟暴露导致的表达改变。

The expression profile of Claudin family members in the developing mouse lung and expression alterations resulting from exposure to secondhand smoke (SHS).

作者信息

Lewis Joshua B, Jimenez Felix R, Merrell Brigham J, Kimbler Brent, Arroyo Juan A, Reynolds Paul R

机构信息

a Department of Physiology and Developmental Biology, Lung and Placenta Research Laboratory , Brigham Young University , Provo , Utah , USA.

出版信息

Exp Lung Res. 2018 Feb;44(1):13-24. doi: 10.1080/01902148.2017.1409846. Epub 2018 Jan 11.

Abstract

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.

摘要

闭合蛋白是紧密连接蛋白,与细胞极性和上皮屏障维持有关。闭合蛋白调控异常会对细胞分化和增殖的发育方面产生不利影响。当前研究评估了闭合蛋白1 - 11和18在胚胎期(E)14.5、16.5和18.5以及出生后第3天(PN)和第15天发育中的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,以定性评估闭合蛋白的蛋白表达。怀孕母鼠从胚胎期(E)15.5至18.5进一步暴露于二手烟(SHS),并立即筛选幼鼠肺中的闭合蛋白mRNA。除了闭合蛋白-6外,闭合蛋白家族成员的mRNA表达模式在E16.5时趋于下降,在E18.5时上升,在PN3时再次下降,然后在PN15时达到表达峰值。闭合蛋白-6的mRNA表达在整个妊娠期和出生后阶段都下降。免疫组织化学分析表明,一部分闭合蛋白可能是近端与远端肺屏障建立的合理协调者。评估SHS暴露后E18.5时的闭合蛋白mRNA表达发现,除了闭合蛋白-18(无变化)外,所有闭合蛋白的转录均显著降低。这些数据支持需要使用敲入/敲除特定闭合蛋白的基因靶向小鼠进行进一步研究,以便确定其在正常和患病肺中的精确功能。

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