2025-10-28 九州大学
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1353
- https://www.kyushu-u.ac.jp/f/63768/25_1028_02.pdf
- https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.24825
アルドステロン産生細胞クラスター形成におけるストレス応答性NR4A2の役割 Role of Stress-Responsive NR4A2 in Aldosterone-Producing Cell Cluster Formation
Norifusa Iwahashi, Hironobu Umakoshi, Yuya Kitamura, Hiroki Kaneko, Masamichi Fujita, Tatsuki Ogasawara, Tazuru Fukumoto, …,and Yoshihiro Ogawa
Hypertension Published 27 October 2025
DOI:https://doi.org/10.1161/HYPERTENSIONAHA.125.24825
Abstract
BACKGROUND:
Aldosterone-producing cell clusters (APCCs), which share some transcriptomic features with aldosterone-producing adenomas, are frequently observed in the adrenal cortex of aged individuals and those with primary aldosteronism. However, the mechanisms driving APCC formation remain poorly understood.
METHODS:
We performed an integrated analysis using spatial transcriptomics and single-cell RNA sequencing of APCC cells, aldosterone-producing adenoma cells, and zona glomerulosa (ZG) cells present in the same adrenal gland of a patient with unilateral primary aldosteronism, with validation analyses conducted on tissue samples from 2 additional patients.
RESULTS:
APCC cells exhibited a distinct cellular population with a gene expression profile more similar to that of the ZG cells than that of aldosterone-producing adenoma cells. In silico perturbation and in vitro studies suggest that the stress-responsive TF (transcription factor) NR4A2 is activated in ZG cells in response to a variety of stresses, such as ACTH (adrenocorticotropic hormone) stimulation, thereby promoting the progression from ZG to APCC cells.
CONCLUSIONS:
Our findings suggest that NR4A2 activation in ZG cells functions as a key molecular mediator in stress-induced APCC formation at least in some cases. Some APCCs maintained ZG-like characteristics with heightened stress responsiveness, representing a distinct cellular state from aldosterone-producing adenomas, which exhibit metabolic reprogramming and enhanced energy metabolism.
