Evidence map›Paper›PMID 28006004›Full record

ArticlePloS one2016

Downregulation of TGF-β Receptor-2 Expression and Signaling through Inhibition of Na/K-ATPase.

Jennifer La, Eleanor Reed, Lan Chan, Larisa V Smolyaninova, Olga A Akomova, Gökhan M Mutlu, Sergei N Orlov, Nickolai O Dulin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  8. The NaCellular and molecular life sciences : CMLS · 2021
    Review
  9. Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery.American journal of physiology. Lung cellular and molecular physiology · 2019
    Article
  10. Review
  11. Review
  12. Article
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  14. Article
  15. Na⁺Molecules (Basel, Switzerland) · 2017
    Review
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

8 authors at 3 institutions in 2 countries.

Jennifer LaDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
Eleanor ReedDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
Lan ChanDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
Larisa V SmolyaninovaLaboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Olga A AkomovaLaboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Gökhan M MutluDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
Sergei N OrlovLaboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Nickolai O DulinDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
University of Chicago · USLomonosov Moscow State University · RUSiberian State Medical University · RU

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Control of myofibroblast activation and pulmonary fibrosis by Na/K-ATPaseR56HL127395 · NHLBI · UNIVERSITY OF CHICAGO · PI DULIN, NICKOLAI O · 2015 to 2015
$389k
NCATS NIH HHS UL1 TR000430NHLBI NIH HHS R56 HL127395
6 · The paper itself

Abstract

Transforming growth factor-beta (TGF-β) is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-β signals through a complex of TGF-β receptors 1 and 2 (TGFβR1 and TGFβR2) that phosphorylate and activate Smad2/3 transcription factors driving transcription of the Smad-target genes. The Na+/K+-ATPase is an integral plasma membrane protein critical for maintaining the electro-chemical gradient of Na+ and K+ in the cell. We found that inhibition of the Na+/K+ ATPase by ouabain results in a dramatic decrease in the expression of TGFβR2 in human lung fibrobalsts (HLF) at the mRNA and protein levels. This was accompanied by inhibition of TGF-β-induced Smad phosphorylation and the expression of TGF-β target genes, such as fibronectin and smooth muscle alpha-actin. Inhibition of Na+/K+ ATPase by an alternative approach (removal of extracellular potassium) had a similar effect in HLF. Finally, treatment of lung alveolar epithelial cells (A549) with ouabain also resulted in the downregulation of TGFβR2, the inhibition of TGF-β-induced Smad phosphorylation and of the expression of mesenchymal markers, vimentin and fibronectin. Together, these data demonstrate a critical role of Na+/K+-ATPase in the control of TGFβR2 expression, TGF-β signaling and cell responses to TGF-β.

Indexed as

Cells, CulturedDown-RegulationFibroblastsHumansLungPhosphorylationProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IISignal TransductionSodium-Potassium-Exchanging ATPaseTransforming Growth Factor betaProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IISodium-Potassium-Exchanging ATPaseTransforming Growth Factor beta

Identifiers

PMID28006004
PMCPMC5179089
OpenAlexW2565290500

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.