ArticleJournal of the American Society of Nephrology : JASN2016
Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Klotho Deficiency Impairs Distal Potassium Homeostasis Through mTORC1-Dependent Suppression of ROMK.Acta physiologica (Oxford, England) · 2026Article
- Visceral Adiposity and Renal Health: From Pathophysiological Mechanisms to Novel Therapeutic Strategies.Journal of clinical medicine · 2026Review
- Biological age acceleration in primary aldosteronism: associations with renin, aldosterone, aldosterone-to-renin ratio, and left ventricular mass index.Journal of hypertension · 2026Article
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Ten Hot Topics in Cardiovascular Risk Management for Chronic Kidney Disease.Cardiorenal medicine · 2026Review
- Hypertension modifies the association between serum Klotho and chronic kidney disease in US adults with diabetes: a cross-sectional study of the NHANES 2007-2016.Renal failure · 2025Article
- Single-Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study.npj aging · 2024Review
- The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study.Preventive medicine reports · 2024Article
- Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice.Endocrinology · 2024Article
- Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping.Science advances · 2024Article
- Extra-adrenal aldosterone: a mini review focusing on the physiology and pathophysiology of intrarenal aldosterone.Endocrine · 2024Review
- Determination of the Relationship Between DNA Methylation Status ofBalkan journal of medical genetics : BJMG · 2023Article
- Urinary Klotho Excretion: A Key Regulator of Sodium Homeostasis in Chronic Kidney Disease Stage 2-4.Medical science monitor basic research · 2023Article
- Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA).Clinical kidney journal · 2023Article
- Antihypertensive treatment with hydrochlorothiazide-hydralazine combination aggravates medial vascular calcification in CKD rats with mineral bone disorder.Frontiers in cardiovascular medicine · 2023Article
- In Vivo Cardiac-specific Expression of Adenylyl Cyclase 4 Gene Protects against Klotho Deficiency-induced Heart Failure.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Aldosterone-Regulated Sodium Transport and Blood Pressure.Frontiers in physiology · 2022Review
- Klotho deficiency-induced arterial calcification involves osteoblastic transition of VSMCs and activation of BMP signaling.Journal of cellular physiology · 2022Article
- Fibroblast growth factor 23-Klotho and hypertension: experimental and clinical mechanisms.Pediatric nephrology (Berlin, Germany) · 2021Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis.
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