AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase Cζ

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Abstract

Interactions between astrocytes and blood vessels are essential for the formation and maintenance of the blood-neural barrier (BNB). Astrocyte-derived A-kinase anchor protein 12 (AKAP12) influences BNB formation, but the mechanism of regulation of BNB functions by AKAP12 is not fully understood. We have defined a new pathway of barriergenesis in human retina microvascular endothelial cells (HRMECs) involving astrocytic AKAP12. Treatment of HRMECs with conditioned media from AKAP12-overexpressing astrocytes reduced phosphorylation of protein kinase Cζ (PKCζ), decreased the levels of vascular endothelial growth factor (VEGF) mRNA and protein, and increased thrombospondin-1 (TSP-1) levels, which led to antiangiogenesis and barriergenesis. Transfection of a small interference RNA targeting PKCζ decreased VEGF levels and increased TSP-1 levels in HRMECs. Rho is a putative downstream signal of PKCζ, and inhibition of Rho kinase with a specific inhibitor, Y27632, decreased VEGF levels and increased TSP-1 levels. We therefore suggest that AKAP12 in astrocytes differentially regulates the expression of VEGF and TSP-1 via the inhibition of PKCζ phosphorylation and Rho kinase activity in HRMECs. © 2008 The Authors.

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Choi, Y. K., & Kim, K. W. (2008). AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase Cζ. FEBS Journal, 275(9), 2338–2353. https://doi.org/10.1111/j.1742-4658.2008.06387.x

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