ArticleJournal of the American Society of Nephrology : JASN2011
Af17 deficiency increases sodium excretion and decreases blood pressure.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide.Journal of translational medicine · 2012Trial
- Epigenetic mechanisms of salt-sensitive hypertension.Clinical kidney journal · 2025Review
- Roles and mechanisms of histone methylation in vascular aging and related diseases.Clinical epigenetics · 2025Review
- Histone Modifications and Their Contributions to Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Aldosterone-Regulated Sodium Transport and Blood Pressure.Frontiers in physiology · 2022Review
- Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
- Loss of Histone H3 K79 Methyltransferase Dot1l Facilitates Kidney Fibrosis by Upregulating Endothelin 1 through Histone Deacetylase 2.Journal of the American Society of Nephrology : JASN · 2020Article
- Epigenetic Mechanisms and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Highly tamoxifen-inducible principal cell-specific Cre mice with complete fidelity in cell specificity and no leakiness.American journal of physiology. Renal physiology · 2018Article
- High-throughput screening identifies FAU protein as a regulator of mutant cystic fibrosis transmembrane conductance regulator channel.The Journal of biological chemistry · 2018Article
- Dot1l deficiency leads to increased intercalated cells and upregulation of V-ATPase B1 in mice.Experimental cell research · 2016Article
- Epigenetics of epithelial Na(+) channel-dependent sodium uptake and blood pressure regulation.World journal of nephrology · 2015Review
- Regulation of αENaC transcription.Vitamins and hormones · 2015Review
- Emerging role of the calcium-activated, small conductance, SK3 K+ channel in distal tubule function: regulation by TRPV4.PloS one · 2014Article
- Mineralocorticoid receptor antagonizes Dot1a-Af9 complex to increase αENaC transcription.American journal of physiology. Renal physiology · 2013Article
- Aldosterone-dependent trans-activation and epigenetic derepression of ENaC: where is the balance?American journal of physiology. Renal physiology · 2013Article
- Epigenetics and the control of the collecting duct epithelial sodium channel.Seminars in nephrology · 2013Review
- An Af9 cis-element directly targets Dot1a to mediate transcriptional repression of the αENaC gene.American journal of physiology. Renal physiology · 2013Article
- Aqp2-expressing cells give rise to renal intercalated cells.Journal of the American Society of Nephrology : JASN · 2013Article
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Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The putative transcription factor AF17 upregulates the transcription of the epithelial sodium channel (ENaC) genes, but whether AF17 modulates sodium homeostasis and BP is unknown. Here, we generated Af17-deficient mice to determine whether deletion of Af17 leads to sodium wasting and low BP. Compared with wild-type mice, Af17-deficient mice had lower BP (11 mmHg), higher urine volume, and increased sodium excretion despite mildly increased plasma concentrations of aldosterone. Deletion of Af17 led to increased dimethylation of histone H3 K79 and reduced ENaC function. The attenuated function of ENaC resulted from decreased ENaC mRNA and protein expression, fewer active channels, lower open probability, and reduced effective activity. In contrast, inducing high levels of plasma aldosterone by a variety of methods completely compensated for Af17 deficiency with respect to sodium handling and BP. Taken together, these data identify Af17 as a potential locus for the maintenance of sodium and BP homeostasis and suggest that a particular histone modification is directly linked to these processes. Af17-mediated regulation of BP is largely, but not exclusively, the result of modulating ENaC, suggesting it has potential as a therapeutic target for the control of BP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.