Evidence map›Paper›PMID 23867654›Full record

ArticleExperimental & molecular medicine2013

Reactive oxygen species regulate context-dependent inhibition of NFAT5 target genes.

Nam-Hoon Kim, Bong-Ki Hong, Soo Youn Choi, Hyug Moo Kwon, Chul-Soo Cho, Eugene C Yi, Wan-Uk Kim

Abstract read
In one paragraph

Article in Experimental & molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
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

23 citing papers in PubMed.

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  13. Mitochondria-Modulating Porous Se@SiOInternational journal of nanomedicine · 2020
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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

7 authors.

Nam-Hoon KimResearch Institute of Immunobiology, Catholic Research Institute of Medical Science, Seoul, Korea.
Bong-Ki Hong
Soo Youn Choi
Hyug Moo Kwon
Chul-Soo Cho
Eugene C Yi
Wan-Uk Kim

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The activation of nuclear factor of activated T cells 5 (NFAT5), a well-known osmoprotective factor, can be induced by isotonic stimuli, such as activated Toll-like receptors (TLRs). It is unclear, however, how NFAT5 discriminates between isotonic and hypertonic stimuli. In this study we identified a novel context-dependent suppression of NFAT5 target gene expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) or a high salt (NaCl) concentration. Although LPS and NaCl both used NFAT5 as a core transcription factor, these stimuli mutually inhibited distinct sets of NFAT5 targets within the cells. Although reactive oxygen species (ROS) are essential for this inhibition, the source of ROS differed depending on the context: mitochondria for high salt and xanthine oxidase for TLRs. Specifically, the high salt-induced suppression of interleukin-6 (IL-6) production was mediated through the ROS-induced inhibition of NFAT5 binding to the IL-6 promoter. The context-dependent inhibition of NFAT5 target gene expression was also confirmed in mouse spleen and kidney tissues that were cotreated with LPS and high salt. Taken together, our data suggest that ROS function as molecular sensors to discriminate between TLR ligation and osmotic stimuli in RAW 264.7 macrophages, directing NFAT5 activity toward proinflammatory or hypertonic responses in a context-dependent manner.

Indexed as

Gene Expression RegulationAnimalsInterleukin-6LipopolysaccharidesMacrophagesMaleMannitolMiceMice, Inbred BALB CNF-kappa BPromoter Regions, GeneticProtein BindingReactive Oxygen SpeciesRotenoneSodium ChlorideToll-Like ReceptorsInterleukin-6LipopolysaccharidesMannitolNfat5 protein, mouseNF-kappa BReactive Oxygen SpeciesRotenoneSodium ChlorideToll-Like ReceptorsTranscription Factors

Identifiers

PMID23867654
PMCPMC3731662

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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.