Identification of STC1 as an β-amyloid activated gene in human brain microvascular endothelial cells using cDNA microarray

To explore the molecular basis underlying β-amyloid peptide (Aβ)-induced toxicity in the cerebrovasculature, we performed a cDNA microarray analysis to investigate the transcriptional profile induced by Aβ in human brain microvascular endothelial cells (HBMECs). This study identified 24 differentially expressed genes in HBMECs upon Aβ treatment. Among these genes, we found that the gene for a well-characterized calcium-regulating hormone, stanniocalcin-1 (STC1) was specifically up-regulated by Aβ treatment in a time and dose-dependent manner. Moreover, using overexpression and knock-down strategies, we found that overexpression of STC1 decreased transmigration of monocytes induced by Aβ and prevented Aβ-induced apoptosis of HBMECs. In addition, we explored the possible mechanisms underlying the effects of STC1, showing that overexpression of STC1 attenuated the effect of Aβ on up-regulating early growth response-1 (Egr-1), macrophage inflammatory protein-1β (MIP-1β), or cleaved caspase-8. Our data thus indicate a key role of STC1 in the response of HBMECs to Aβ exposure.