CASZ1: a promising factor modulating aldosterone biosynthesis and mineralocorticoid receptor activity

Kenichi Yokota, Hirotaka Shibata, Isao Kurihara, Hiroshi Itoh, Masakatsu Sone

Research output: Contribution to journalShort surveypeer-review

2 Citations (Scopus)

Abstract

Hypertension is the definitive risk factor for cardiovascular disease. Primary aldosteronism (PA), a typical form of secondary hypertension, is responsible for treatment-resistant hypertension and carries an even higher risk of causing cardiovascular complications than essential hypertension. Several genes involved in the pathogenesis of hypertension have been identified recently using genome-wide association studies (GWASs). Among these, castor zinc finger 1(CASZ1) is considered to be involved in the pathophysiology of hypertension via modulation of aldosterone action. In 2021, using a biochemical approach with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified CASZ1b, an isoform of CASZ1, as a novel mineralocorticoid receptor (MR) coregulator. Our further analysis revealed that CASZ1b is coexpressed with MR in MR targets such as kidney tubule cells, and that a decrease in CASZ1 protein levels promotes aldosterone-dependent transcriptional activity of MR. Further, a recent study of GWAS on PA identified CASZ1 to be a PA-related gene and demonstrated that overexpression of CASZ1 suppresses aldosterone biosynthesis in adrenal cells. These results suggest CASZ1 plays a pivotal role in the pathophysiology of hypertension and PA via dual mechanisms: aldosterone biosynthesis and transcriptional activity of MR. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)417-420
Number of pages4
JournalHypertension Research
Volume46
Issue number2
DOIs
Publication statusPublished - 2023 Feb

Keywords

  • Aldosteone
  • CASZ1
  • Hypertension
  • Mineralocorticoid receptor
  • Primary aldosteronism

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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