Evidence map›Paper›PMID 25617622›Full record

ArticlePloS one2015

RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFα.

Sara R Savage, Colin A Bretz, John S Penn

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. RF/6A Chorioretinal Cells Do Not Display Key Endothelial Phenotypes.Investigative ophthalmology & visual science · 2018
    Article
  11. Article
  12. IPCellular and molecular life sciences : CMLS · 2017
    Review
  13. Article
  14. 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

3 authors at 1 institution in 1 country.

Sara R SavageDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Colin A BretzDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
John S PennDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Vanderbilt University · US

Funding

The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007628 · NIGMS · VANDERBILT UNIVERSITY · PI BARNETT, JOEY VICTOR, KAVALALI, EGE T · 1985 to 2022
$11.2M
RETINOPATHY OF PREMATURITY--UNDERSTAND ITS PATHOGENESISR01EY007533 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PENN, JOHN S. · 1993 to 2018
$7.0M
The calcineurin/NFAT signaling axis in diabetic retinopathy pathogenesisR01EY023639 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PENN, JOHN S. · 2014 to 2017
$1.8M
LSM880-Airyscan Confocal Microscope for Large Shared ResourceS10OD021630 · OD · VANDERBILT UNIVERSITY · PI WELLS, K. SAM · 2016 to 2016
$560k
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1TR000445NEI NIH HHS P30 EY008126NEI NIH HHS P30-EY08126NEI NIH HHS R01 EY007533NEI NIH HHS R01 EY023639NEI NIH HHS R01-EY023639NEI NIH HHS R01-EY07533NIGMS NIH HHS T32 GM007628NIGMS NIH HHS T32-GM007628NIH HHS S10 OD021630
6 · The paper itself

Abstract

TNFα has been identified as playing an important role in pathologic complications associated with diabetic retinopathy and retinal inflammation, such as retinal leukostasis. However, the transcriptional effects of TNFα on retinal microvascular endothelial cells and the different signaling pathways involved are not yet fully understood. In the present study, RNA-seq was used to profile the transcriptome of human retinal microvascular endothelial cells (HRMEC) treated for 4 hours with TNFα in the presence or absence of the NFAT-specific inhibitor INCA-6, in order to gain insight into the specific effects of TNFα on RMEC and identify any involvement of NFAT signaling. Differential expression analysis revealed that TNFα treatment significantly upregulated the expression of 579 genes when compared to vehicle-treated controls, and subsequent pathway analysis revealed a TNFα-induced enrichment of transcripts associated with cytokine-cytokine receptor interactions, cell adhesion molecules, and leukocyte transendothelial migration. Differential expression analysis comparing TNFα-treated cells to those co-treated with INCA-6 revealed 10 genes whose expression was significantly reduced by the NFAT inhibitor, including those encoding the proteins VCAM1 and CX3CL1 and cytokines CXCL10 and CXCL11. This study identifies the transcriptional effects of TNFα on HRMEC, highlighting its involvement in multiple pathways that contribute to retinal leukostasis, and identifying a previously unknown role for NFAT-signaling downstream of TNFα.

Indexed as

RetinaSequence Analysis, RNADiabetic RetinopathyEndothelial CellsHumansMicrovesselsMolecular Targeted TherapyNFATC Transcription FactorsSignal TransductionTranscriptomeTumor Necrosis Factor-alphaNFATC Transcription FactorsTumor Necrosis Factor-alpha

Identifiers

PMID25617622
PMCPMC4305319
OpenAlexW2003437963

What OpenQuestion holds

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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.