Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism
| Autor: | Livia Lenzini, Lucia Petrelli, Juerg Nussberger, Teresa Maria Seccia, William E. Rainey, Giulio Ceolotto, Anna S. Belloni, C Recarti, Abril Gonzales-Campos, Brasilina Caroccia, Gian Paolo Rossi |
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| Přispěvatelé: | Pathologie, RS: CARIM - R2 - Cardiac function and failure, RS: CARIM - R3 - Vascular biology |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Functional role
Adenoma Adult Male medicine.medical_specialty Physiology MAP Kinase Signaling System Receptors Cell Surface Real-Time Polymerase Chain Reaction Rats Sprague-Dawley Primary aldosteronism Internal medicine Cell Line Tumor Renin–angiotensin system Adrenal Glands Hyperaldosteronism Internal Medicine medicine Animals Cytochrome P-450 CYP11B2 Humans In patient Receptor Aldosterone ATP6AP2 primary aldosteronism business.industry fungi medicine.disease Adrenal Cortex Neoplasms Rats medicine.anatomical_structure Endocrinology Real-time polymerase chain reaction adrenal renin Zona glomerulosa Case-Control Studies Hypertension Female Zona Glomerulosa prorenin receptor Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Hypertension, 33(5), 1014-1022. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1473-5598 0263-6352 |
| DOI: | 10.1097/HJH.0000000000000504 |
| Popis: | 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, CD56R 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. |
| Databáze: | OpenAIRE |
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