biBackground /i/bPIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity. biMethods /i/biPim1-/-/iMAEC were isolated from iPim1 /iknockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis. biResults /i/biPim1-/-/iMAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of iPim1/i- cDNA into iPim1-/-/iMAEC significantly restored wildtype adhesive characteristics. iPim1-/--/iMAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and β-catenin, respectively. Junctional molecules such as iCadherin 13 /iand matrix components such as iCollagen 6a3 /iwere highly upregulated in iPim1-/- /icells. Intriguingly, extracellular matrix deposited by iPim1-/- /icells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells. biConclusion /i/bLoss of iPim1 /iinduces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.
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