Protein Phosphatase 1 Beta is Modulated by Chronic XXXX and Involved in the Angiogenic Endothelial Cell Migration.

@entity5 @entity13977 @entity6286 @entity519 @entity1562
BACKGROUND/AIM: Endothelial cell migration is required for physiological angiogenesis, but also contributes to various pathological conditions, including @entity5 vascularization. The mRNA expression of PP1cb, the beta isoform of the catalytic @entity13977 subunit, was shown to be upregulated in chronic @entity519 . Since @entity519 is a major regulator of angiogenesis, the potential role of @entity13977 cb in angiogenesis was investigated. METHODS: We examined PP1cb protein level in pediatric heart following chronic @entity519 and found @entity13977 cb upregulation in cyanotic compared with @entity1562 . By treating HUVEC cells with @entity519 mimicking agent, PP1cb protein level increased with maximum at 8 hours. The effect of @entity13977 cb pharmacological inhibition, knockdown and overexpression, on endothelial cell migration and morphogenesis, was examined using in vitro wound healing scratch assay and endothelial tube formation assay. The @entity13977 cb knockdown effects on F-actin reorganization ( @entity6286 staining), focal adhesion formation (vinculin) and focal adhesion kinases (FAK) activation, were evaluated by immunocytochemical staining and immunoblotting with specific antibodies. RESULTS: @entity13977 cb knockdown significantly reduces endothelial cell migration, but does not have any significant effect on endothelial tube formation. Endothelial cell migration in the knockdown group is restored to the control level upon consecutive transfection with @entity13977 cb cDNA. PP1cb overexpression does not significantly affect endothelial cell migration. Furthermore, @entity13977 cb knockdown induces profound cytoskeletal reorganization, loss of focal adhesion sites and impairment of focal adhesion kinases (FAK) activation. CONCLUSIONS: @entity13977 cb is regulator of endothelial cell migration, which is critical in the angiogenic process. @entity13977 cb inhibition reduces endothelial cell migration through focal adhesion turnover and actin polymerization pathways.    2015 S. Karger AG, Basel.
