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Cellular Senescence in Human Aldosterone-Producing Adrenocortical Cells and Related Disorders

Authors :
Jacopo Pieroni
Yuto Yamazaki
Xin Gao
Yuta Tezuka
Hiroko Ogata
Kei Omata
Yoshikiyo Ono
Ryo Morimoto
Yasuhiro Nakamura
Fumitoshi Satoh
Hironobu Sasano
Source :
Biomedicines, Vol 9, Iss 5, p 567 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

In situ cortisol excess was previously reported to promote cellular senescence, a cell response to stress, in cortisol-producing adenomas (CPA). The aim of this study was to explore senescence pathways in aldosterone-producing cells and related disorders, and the influence of aldosterone overproduction on in situ senescence. We analyzed 30 surgical cases of aldosterone-producing adenoma (APA), 10 idiopathic hyperaldosteronism (IHA) and 19 normal adrenals (NA). CYP11B2 and senescence markers p16 and p21 were immunolocalized in all those cases above and results were correlated with histological/endocrinological findings. In the three cohorts examined, the zona glomerulosa (ZG) was significantly more senescent than other corticosteroid-producing cells. In addition, the ZG of adjacent non-pathological adrenal glands of APA and IHA had significantly higher p16 expression than adjacent non-pathological zona fasciculata (ZF), reticularis (ZR) and ZG of NA. In addition, laboratory findings of primary aldosteronism (PA) were significantly correlated with p21 status in KCNJ5-mutated tumors. Results of our present study firstly demonstrated that non-aldosterone-producing cells in the ZG were the most senescent compared to other cortical zones and aldosterone-producing cells in PA. Therefore, aldosterone production, whether physiological or pathological, could be maintained by suppression of cell senescence in human adrenal cortex.

Details

Language :
English
ISSN :
22279059
Volume :
9
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.9ac7cde585b743c8b56e5057637836a6
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines9050567