Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism.

Détails

ID Serval
serval:BIB_E4E3B00C2895
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism.
Périodique
Journal of Hypertension
Auteur⸱e⸱s
Recarti C., Seccia T.M., Caroccia B., Gonzales-Campos A., Ceolotto G., Lenzini L., Petrelli L., Belloni A.S., Rainey W.E., Nussberger J., Rossi G.P.
ISSN
1473-5598 (Electronic)
ISSN-L
0263-6352
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
33
Numéro
5
Pages
1014-1022
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
OBJECTIVES: Prorenin can be detected in plasma of hypertensive patients. If detected in patients with primary aldosteronism could implicate prorenin in the development of primary aldosteronism. To address this issue, we measured the plasma prorenin levels in primary aldosteronism patients, the expression of the prorenin receptor (PRR) in the normal human adrenocortical zona glomerulosa and aldosterone-producing adenoma (APA), and we investigated the functional effects of PRR activation in human adrenocortical cells.
METHOD: Plasma renin activity, aldosterone, and active and total trypsin-activated renin were measured in primary aldosteronism patients, essential hypertensive patients, and healthy individuals, and then prorenin levels were calculated. Localization and functional role of PRR were investigated in human and rat tissues, and aldosterone-producing cells.
RESULTS: Primary aldosteronism patients had detectable plasma levels of prorenin. Using digital-droplet real-time PCR, we found a high PRR-to-porphobilinogen deaminase ratio in both the normal adrenal cortex and APAs. Marked expression of the PRR gene and protein was also found in HAC15 cells. Immunoblotting, confocal, and immunogold electron microscopy demonstrated PRR at the cell membrane and intracellularly. Renin and prorenin significantly triggered both CYP11B2 expression (aldosterone synthase) and ERK1/2 phosphorylation, but only CYP11B2 transcription was prevented by aliskiren.
CONCLUSION: The presence of detectable plasma prorenin in primary aldosteronism patients, and the high expression of PRR in the normal human adrenal cortex, APA tissue, CD56+ aldosterone-producing cells, along with activation of CYP11B2 synthesis and ERK1/2 phosphorylation, suggest that the circulating and locally produced prorenin may contribute to the development or maintenance of human primary aldosteronism.
Mots-clé
Adenoma/metabolism, Adrenal Cortex Neoplasms/metabolism, Adrenal Glands/metabolism, Adult, Aldosterone/biosynthesis, Animals, Case-Control Studies, Cell Line, Tumor, Cytochrome P-450 CYP11B2/metabolism, Female, Humans, Hyperaldosteronism/blood, Hyperaldosteronism/etiology, Hypertension/blood, MAP Kinase Signaling System, Male, Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, Receptors, Cell Surface/blood, Receptors, Cell Surface/genetics, Renin/metabolism, Zona Glomerulosa/metabolism
Pubmed
Web of science
Création de la notice
20/02/2015 10:59
Dernière modification de la notice
20/08/2019 16:08
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