VEGF stimulates RCAN1.4 expression in endothelial cells via a pathway requiring Ca2+/calcineurin and protein kinase C-delta.

PloS One
Katherine HolmesMichael J Cross

Abstract

Vascular endothelial growth factor (VEGF) has previously been shown to upregulate the expression of the endogenous calcineurin inhibitor, regulator of calcineurin 1, variant 4 (RCAN1.4). The aim of this study was to determine the role and regulation of VEGF-mediated RCAN1.4 expression, using human dermal microvascular endothelial cells (HDMECs) as a model system. We show that VEGF is able to induce RCAN1.4 expression during cellular proliferation and differentiation, and that VEGF-mediated expression of RCAN1.4 was inhibited by the use of inhibitors to protein kinase C (PKC) and calcineurin. Further analysis revealed that siRNA silencing of PKC-delta expression partially inhibited VEGF-stimulated RCAN1.4 expression. Knockdown of RCAN1.4 with siRNA resulted in a decrease in cellular migration and disrupted tubular morphogenesis when HDMECs were either stimulated with VEGF in a collagen gel or in an endothelial/fibroblast co-culture model of angiogenesis. Analysis of intracellular signalling revealed that siRNA mediated silencing of RCAN1.4 resulted in increased expression of specific nuclear factor of activated T-cells (NFAT) regulated genes. Our data suggests that RCAN1.4 expression is induced by VEGFR-2 activation in a Ca(2+) ...Continue Reading

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Citations

Jan 8, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yoanne MousseauFranck G Sturtz
Oct 20, 2010·The Journal of Biological Chemistry·Katarzyna A UniewiczDavid G Fernig
Nov 9, 2012·Journal of Biomedical Materials Research. Part a·María Belén Sánchez-IlárduyaEduardo Anitua
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Feb 13, 2016·Biomarkers in Medicine·Chen-Ming SuChih-Hsin Tang
May 23, 2021·In Vitro Cellular & Developmental Biology. Animal·Siti Nurnasihah Md HashimAhmad Azlina

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Methods Mentioned

BETA
transgenic
FCS
PCR
transfection
Assay
transfections
PMA

Software Mentioned

AngioQuant

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