Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function
Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function
复制标题
紧密连接蛋白-3（Claudin-3）和紧密连接蛋白-4（Claudin-4）对肺泡上皮屏障功能的不同影响
DOI：
10.1152/ajplung.00299.2010
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发表时间：
2011-07-01
影响因子：
4.9
通讯作者：
Koval, Michael
中科院分区：
文献类型：
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作者：
Mitchell, Leslie A.;Overgaard, Christian E.;Koval, Michael
[10]杨文辉，李文辉. claudin-3和claudin-4对肺泡上皮屏障功能的不同影响。美国生理学杂志肺细胞分子生理学301：L40-L49，2011年。首次发表于2011年4月22日; doi：10.1152/ajplung.00299.2010.-肺泡屏障功能主要依赖于紧密连接蛋白家族。在由肺泡上皮细胞表达的主要密封蛋白中，密封蛋白（Cldn）-3和Cldn-4通过氨基酸同源性最密切相关，但它们在表达模式上显著不同。先前发表的报道已经表明，Cldn-3主要由II型肺泡上皮细胞表达; Cldn-4在整个肺泡上皮中表达，并且响应于急性肺损伤而特异性上调。使用用黄色荧光蛋白标记的claudin构建体转导的原代大鼠肺泡上皮细胞，我们已经确定了Cldn-3和Cldn-4在肺泡上皮屏障功能中的作用。令人惊讶的是，增加Cldn-3的表达降低肺泡上皮屏障功能，通过跨上皮阻力和染料通量测量评估。相反，与对照细胞相比，增加Cldn-4表达改善肺泡上皮细胞跨上皮阻力。其他肺泡上皮紧密连接蛋白在很大程度上不受Cldn-3和Cldn-4表达增加的影响。总之，这些结果表明，在肺泡上皮的情况下，Cldn-3和Cldn-4对细胞旁通透性具有不同的影响，尽管它们的细胞外环结构域具有显著的同源性。
Mitchell LA, Overgaard CE, Ward C, Margulies SS, Koval M. Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function. Am J Physiol Lung Cell Mol Physiol 301: L40-L49, 2011. First published April 22, 2011; doi: 10.1152/ajplung.00299.2010.-Alveolar barrier function depends critically on the claudin family tight junction proteins. Of the major claudins expressed by alveolar epithelial cells, claudin (Cldn)-3 and Cldn-4 are the most closely related by amino acid homology, yet they differ dramatically in the pattern of expression. Previously published reports have shown that Cldn-3 is predominantly expressed by type II alveolar epithelial cells; Cldn-4 is expressed throughout the alveolar epithelium and is specifically upregulated in response to acute lung injury. Using primary rat alveolar epithelial cells transduced with yellow fluorescent protein-tagged claudin constructs, we have identified roles for Cldn-3 and Cldn-4 in alveolar epithelial barrier function. Surprisingly, increasing expression of Cldn-3 decreased alveolar epithelial barrier function, as assessed by transepithelial resistance and dye flux measurements. Conversely, increasing Cldn-4 expression improved alveolar epithelial transepithelial resistance compared with control cells. Other alveolar epithelial tight junction proteins were largely unaffected by increased expression of Cldn-3 and Cldn-4. Taken together, these results demonstrate that, in the context of the alveolar epithelium, Cldn-3 and Cldn-4 have different effects on paracellular permeability, despite significant homology in their extracellular loop domains.