Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis
Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis
复制标题
Claudin-5通过改变脑微血管内皮细胞增殖、迁移和粘附来调节血脑屏障通透性，预防肺癌转移
DOI：
10.1111/cns.12764
复制
发表时间：
2017-12-01
影响因子：
5.5
通讯作者：
Jiang, Wen-Guo
中科院分区：
文献类型：
--
作者：
Ma, Shun-Chang;Li, Qi;Jiang, Wen-Guo
目的：探讨Claudin-5（CLDN5）在肺癌脑转移过程中对血脑屏障（BBB）通透性的调节作用。通过在人脑血管内皮细胞中沉默和过表达CLDN5基因，（hCMEC/D3）细胞，我们证明了在CLDN5过表达的hCMEC/cLDN5中细胞迁移能力的减弱和CLDN5在细胞增殖中的显著的积极作用。在CLDN5敲除组中观察到相反的结果。CLDN5的表达增强可降低hCMEC/D3细胞的细胞外通透性，降低肺腺癌A549细胞的侵袭能力。总体上，使用Affyscore Human Transcriptome Array 2.0（HTA 2.0）发现1685个基因在CLDN5过表达细胞和对照细胞之间差异表达，并且通过基因本体论和途径分析确定这些基因的功能。这1685个基因可能的生物学功能包括细胞增殖、粘附分子以及Jak-STAT、PI3K-Akt、Wnt和Notch信号通路。结论：CLDN5通过调节hCMEC/D3细胞的增殖、迁移和通透性，特别是通过细胞粘附分子信号通路，增强紧密连接的功能，从而参与了对血脑屏障通透性的调节，从而减少了肺癌脑转移的形成。
Aims: To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis.Results: By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group. The reinforced CLDN5 expression reduced the paracellular permeability of hCMEC/D3 cells and decreased the invasion of lung adenocarcinoma A549 cells. Overall, 1685 genes were found to be differentially expressed between the CLDN5-overexpressing cells and the control cells using the Affymetrix Human Transcriptome Array 2.0 (HTA 2.0), and the function of these genes was determined by Gene Ontology and pathway analyses. The possible biological functions of the 1685 genes include cell proliferation, adhesion molecules, and the Jak-STAT, PI3K-Akt, Wnt, and Notch signaling pathways. The identified sets of mRNAs that were specific to CLDN5-overexpressing hCMEC/D3 cells were verified by a qRT-PCR experiment.Conclusion: CLDN5 regulates the permeability of BBB by regulating the proliferation, migration, and permeability of hCMEC/D3 cells, especially through the cell adhesion molecule signaling pathway, to enhance the function of the tight junctions, which was involved in reducing the formation of lung cancer brain metastasis.