Evidence for the involvement of endothelial cell products in adrenal CITED2 expression |
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Authors: | Matthias Haase Ishrath Ansurudeen Sven Schinner Iryna Paramonova Matthias Schott Claudia Papewalis Stefan R Bornstein Werner A Scherbaum Holger S Willenberg |
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Institution: | (1) Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany;(2) Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden;(3) Department of Medicine III, Carl Gustav Carus Medical School, University of Technology, Dresden, Germany |
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Abstract: | The adrenal gland contains a well-organized network of blood vessels, and adrenocortical cells are situated in close proximity
to endothelial cells. Recently, several new mechanisms have been characterized that control the release of aldosterone by
adrenocortical cells, including the involvement of endothelial-cell-derived factors. Interestingly, a CBP/p300-interacting
transactivator with ED-rich tail 2 (CITED2), which is necessary for adrenal development, has been linked to aldosterone synthesis.
We have therefore examined the effects of endothelial-cell-conditioned medium (ECCM), as produced during the incubation of
human umbilical vein endothelial cells for 24 h, on the promoter activity and mRNA and protein expression of CITED2 in adrenocortical
cells as represented by the NCI-H295R cell line. We have found a dose-dependent effect of ECCM on CITED2 promoter activity;
this peaks at 480%. Activation of the CITED2 promoter occurs in parallel to an increase in CITED2 messenger RNA (as quantified
by real-time polymerase chain reaction) and protein. The stimulatory effect of ECCM can be reversed by blocking mitogen-activated
protein kinase activity with the MEK1-inhibitor PD98059. We conclude that products secreted by endothelial cells control not
only steroidogenesis, but also factors that are important for adrenocortical development, thereby highlighting the role of
cellular interactions within adrenocortical development and physiology.
This work was supported by a grant from the Doktor Robert Pfleger-Stiftung, Bamberg, Germany, to H.S.W. |
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Keywords: | CITED2 Adrenal Aldosterone Hypertension Organogenesis Human Mouse |
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