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AKAP12 in astrocytes induces barrier functions in human endothelial cells through protein kinase Cζ
Author(s) -
Choi Yoon Kyung,
Kim KyuWon
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06387.x
Subject(s) - protein kinase c , microbiology and biotechnology , phosphorylation , protein kinase a , astrocyte , kinase , chemistry , transfection , vascular endothelial growth factor , angiogenesis , biology , biochemistry , cancer research , endocrinology , vegf receptors , central nervous system , gene
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.