Evidence map›Paper›PMID 33219307›Full record

ArticleScientific reports2020

Chronic exposure to TNF reprograms cell signaling pathways in fibroblast-like synoviocytes by establishing long-term inflammatory memory.

Umesh Gangishetti, Sergio Ramirez-Perez, Kyle Jones, Abul Arif, Hicham Drissi, Pallavi Bhattaram

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Umesh GangishettiDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Sergio Ramirez-PerezDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Kyle JonesDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Abul ArifDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Hicham DrissiDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Pallavi BhattaramDepartment of Orthopaedics, Emory University School of Medicine, Atlanta, GA, 30322, USA. pallavi.bhattaram@emory.edu.
Emory University · USAtlanta VA Medical Center · US

Funding

Uncovering the role of Setbp1 in fibroblast-like synoviocytes during inflammatory arthritisR01AR070736 · NIAMS · EMORY UNIVERSITY · PI Pallavi Bhattaram · 2017 to 2026
$3.0M
NIAMS NIH HHS R01 AR070736
6 · The paper itself

Abstract

Fibroblast-like synoviocytes (FLS) play a critical role in the pathogenesis of rheumatoid arthritis (RA). Chronic inflammation induces transcriptomic and epigenetic modifications that imparts a persistent catabolic phenotype to the FLS, despite their dissociation from the inflammatory environment. We analyzed high throughput gene expression and chromatin accessibility data from human and mouse FLS from our and other studies available on public repositories, with the goal of identifying the persistently reprogrammed signaling pathways driven by chronic inflammation. We found that the gene expression changes induced by short-term tumor necrosis factor-alpha (TNF) treatment were largely sustained in the FLS exposed to chronic inflammation. These changes that included both activation and repression of gene expression, were accompanied by the remodeling of chromatin accessibility. The sustained activated genes (SAGs) included established pro-inflammatory signaling components known to act at multiple levels of NF-kappaB, STAT and AP-1 signaling cascades. Interestingly, the sustained repressed genes (SRGs) included critical mediators and targets of the BMP signaling pathway. We thus identified sustained repression of BMP signaling as a unique constituent of the long-term inflammatory memory induced by chronic inflammation. We postulate that simultaneous targeting of these activated and repressed signaling pathways may be necessary to combat RA persistence.

Indexed as

AnimalsArthritis, RheumatoidBone Morphogenetic ProteinsCells, CulturedDatasets as TopicEpigenesis, GeneticFibroblastsHumansMicePrimary Cell CultureRecombinant ProteinsRNA-SeqSignal TransductionSTAT Transcription FactorsSynovial MembraneSynoviocytesBone Morphogenetic ProteinsRecombinant ProteinsSTAT Transcription FactorsTNF protein, humanTranscription Factor AP-1Tumor Necrosis Factor-alpha

Identifiers

PMID33219307
PMCPMC7679373
OpenAlexW3104443511

What OpenQuestion holds

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LicenceCC BY
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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.