Evidence map›Paper›PMID 25776071›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion.

Junhua Zhou, Lalarukh Haris Shaikh, Sudeshna G Neogi, Ian McFarlane, Wanfeng Zhao, Nichola Figg, Cheryl A Brighton, Carmela Maniero, Ada E D Teo, Elena A B Azizan and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  6. Effects of intron conversion in the humanThe Journal of biological chemistry · 2020
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  16. Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations.The New England journal of medicine · 2015
    Article
  17. Article
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

11 authors at 2 institutions in 1 country.

Junhua ZhouFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Lalarukh Haris ShaikhFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Sudeshna G NeogiFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Ian McFarlaneFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Wanfeng ZhaoFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Nichola FiggFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Cheryl A BrightonFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Carmela ManieroFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Ada E D TeoFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Elena A B AzizanFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.).
Morris J BrownFrom the Clinical Pharmacology Unit, Department of Medicine (J.Z., L.H.S., C.A.B., C.M., A.E.D.T, E.A.B.A., M.J.B.), Cardiovascular Division, Department of Medicine (N.F.), University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Clinical Biochemistry, GenomicsCoreLab, Cambridge NIHR BRC, Department of Clinical Biochemistry (S.G.N., I.M.), and Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust (W.Z.), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia (E.A.B.A.). m.j.brown@cai.cam.ac.uk.
Addenbrooke's Hospital · GBCambridge University Hospitals NHS Foundation Trust · GB

Funding

British Heart Foundation FS/11/35/28871British Heart Foundation FS/14/12/30540British Heart Foundation FS/14/75/31134British Heart Foundation PG/07/085/23349British Heart Foundation SP/08/002/24118Wellcome Trust 085686Wellcome Trust 085687/Z/08/A
6 · The paper itself

Abstract

Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller, zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes >10-fold upregulated in ZG (compared with zona fasciculata) and >10-fold upregulated in aldosterone-producing adenomas (compared with ZG). DACH1, a gene associated with tumor progression, was further analyzed. The role of DACH1 on steroidogenesis, transforming growth factor-β, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1 decreased aldosterone production. Overexpression of DACH1 in H295R cells activated the transforming growth factor-β and canonical Wnt signaling pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of primary human adrenal cells with angiotensin II decreased DACH1 mRNA expression. Interestingly, there was little overlap between our top ZG genes and those in rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from rodent ZG, (2) DACH1 inhibits aldosterone secretion in human adrenals, and (3) transforming growth factor-β signaling pathway is activated in DACH1 overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals.

Indexed as

Gene Expression Regulation, NeoplasticAdrenocortical CarcinomaAldosteroneDisease ProgressionEye ProteinsFemaleHumansImmunohistochemistryMaleMiddle AgedReal-Time Polymerase Chain ReactionRNA, NeoplasmSignal TransductionTranscription FactorsTransforming Growth Factor betaTumor Cells, CulturedAldosteroneDACH1 protein, humanEye ProteinsRNA, NeoplasmTranscription FactorsTransforming Growth Factor betaaldosteroneDACH1 protein, humanhyperaldosteronismtransforming growth factor betazona glomerulosa

Identifiers

PMID25776071
PMCPMC4387203
OpenAlexW2114004604

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.