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

Hypertension Research volume 46, pages 417–420 (2023)Cite this article

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.

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Authors and Affiliations

  1. Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Kenichi Yokota & Masakatsu Sone

  2. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan

    Hirotaka Shibata

  3. Department of Medical Education, National Defense Medical College, Tokorozawa, Japan

    Isao Kurihara

  4. Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Isao Kurihara & Hiroshi Itoh

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  1. Kenichi Yokota
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  2. Hirotaka Shibata
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  5. Masakatsu Sone
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Correspondence to Kenichi Yokota.

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Yokota, K., Shibata, H., Kurihara, I. et al. CASZ1: a promising factor modulating aldosterone biosynthesis and mineralocorticoid receptor activity. Hypertens Res 46, 417–420 (2023). https://doi.org/10.1038/s41440-022-01131-8

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