Evidence map›Paper›PMID 15489962›Full record

ArticleThe Journal of clinical investigation2004

Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression.

Rasoul Alikhani-Koopaei, Fatemeh Fouladkou, Felix J Frey, Brigitte M Frey

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Maternal stress and fetoplacental cortisol regulation in small-for-gestational-age newborns.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2025
    Article
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  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Epigenetics: A Missing Link Between Early Life Stress and Depression.Advances in experimental medicine and biology · 2021
    Review

52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Rasoul Alikhani-KoopaeiDepartment of Nephrology and Hypertension, University Hospital of Berne, Berne UNK 3010, Switzerland.
Fatemeh Fouladkou
Felix J Frey
Brigitte M Frey
University of Bern · CHUniversity Hospital of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11 beta-hydroxyglucocorticoids. Variable activity of 11 beta HSD2 is relevant for blood pressure control and hypertension. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for the rigorous control of expression of the gene encoding 11 beta HSD2, HSD11B2. CpG islands covering the promoter and exon 1 of HSD11B2 were found to be densely methylated in tissues and cell lines with low expression but not those with high expression of HSD11B2. Demethylation induced by 5-aza-2'-deoxycytidine and procainamide enhanced the transcription and activity of the 11 beta HSD2 enzyme in human cells in vitro and in rats in vivo. Methylation of HSD11B2 promoter-luciferase constructs decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including those for Sp1/Sp3, Arnt, and nuclear factor 1 (NF1) diminished their DNA-binding activity. Herein NF1 was identified as a strong HSD11B2 stimulatory factor. The effect of NF1 was dependent on the position of CpGs and the combination of CpGs methylated. A methylated-CpG-binding protein complex 1 transcriptional repression interacted directly with the methylated HSD11B2 promoter. These results indicate a role for DNA methylation in HSD11B2 gene repression and suggest an epigenetic mechanism affecting this gene causally linked with hypertension.

Indexed as

Epigenesis, GeneticPromoter Regions, GeneticTranscription, Genetic11-beta-Hydroxysteroid Dehydrogenase Type 2AnimalsAzacitidineBase SequenceBlood PressureCell Line, TumorCpG IslandsDecitabineDNADNA MethylationEnzyme InhibitorsHumansHydrocortisone11-beta-Hydroxysteroid Dehydrogenase Type 2AzacitidineDecitabineDNAEnzyme InhibitorsHydrocortisoneHydroxamic AcidsProcainamideReceptors, GlucocorticoidTranscription Factorstrichostatin A

Identifiers

PMID15489962
PMCPMC522246
OpenAlexW2066279187

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.