Claudin‐5 regulates blood‐brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis

Summary Aims To investigate the roles of Claudin‐5 ( CLDN 5) in regulating the permeability of the blood‐brain barrier ( BBB ) during lung cancer brain metastasis. Results By silencing and overexpressing the CLDN 5 gene in human brain vascular endothelial ( hCMEC /D3) cells, we demonstrated the attenuation of cell migration ability and CLDN 5's significant positive role in cell proliferation in CLDN 5‐overexpressing hCMEC /D3 cells and observed the opposite result in the CLDN 5 knockdown group. The reinforced CLDN 5 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 CLDN 5‐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 , PI 3K‐Akt, Wnt, and Notch signaling pathways. The identified sets of mRNA s that were specific to CLDN 5‐overexpressing hCMEC /D3 cells were verified by a qRT ‐ PCR experiment. Conclusion CLDN 5 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.