Evidence map›Paper›PMID 24319262›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

The p53 transcription factor modulates microglia behavior through microRNA-dependent regulation of c-Maf.

Wei Su, Stephanie Hopkins, Nicole K Nesser, Bryce Sopher, Aurelio Silvestroni, Simon Ammanuel, Suman Jayadev, Thomas Möller, Jonathan Weinstein, Gwenn A Garden

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.5field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 108 citations in OpenAlex.

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  17. MiR-155: An Important Regulator of Neuroinflammation.International journal of molecular sciences · 2021
    Review
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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

10 authors at 1 institution in 1 country.

Wei SuDepartment of Neurology, University of Washington, Seattle, WA 98195.
Stephanie Hopkins
Nicole K Nesser
Bryce Sopher
Aurelio Silvestroni
Simon Ammanuel
Suman Jayadev
Thomas Möller
Jonathan Weinstein
Gwenn A Garden
University of Washington · US

Funding

Restoring FMRP Phenotypes Frpm Temporal Regional and Splice- Isoforms VarationsP30HD002274 · NICHD · UNIVERSITY OF WASHINGTON · PI GURALNICK, MICHAEL J · 1985 to 2013
$33.6M
Intellectual and Developmental Disabilities Research CenterU54HD083091 · NICHD · UNIVERSITY OF WASHINGTON · PI DOHERTY, DANIEL · 2014 to 2019
$7.9M
Microglial Interferon Signaling and Ischemic PreconditioningR01NS076620 · NINDS · UNIVERSITY OF WASHINGTON · PI WEINSTEIN, JONATHAN R · 2011 to 2015
$1.7M
Molecular Regulation of Microglia BehaviorR01NS073848 · NINDS · UNIVERSITY OF WASHINGTON · PI GARDEN, GWENN A · 2011 to 2016
$1.7M
The Role of p53 in the Regulation of NeuroinflammationR21NS062269 · NINDS · UNIVERSITY OF WASHINGTON · PI GARDEN, GWENN A · 2008 to 2009
$375k
Generation and initial charcterization of a mouse with floxed miR-155 for conditiR03NS070141 · NINDS · UNIVERSITY OF WASHINGTON · PI GARDEN, GWENN A · 2010 to 2011
$154k
NICHD NIH HHS P30 HD002274NICHD NIH HHS P30-HD02274NICHD NIH HHS U54 HD083091NINDS NIH HHS R01 NS073848NINDS NIH HHS R01NS073848NINDS NIH HHS R01 NS076620NINDS NIH HHS R03 NS070141NINDS NIH HHS R03NS70141NINDS NIH HHS R21 NS062269NINDS NIH HHS R21NS062269
6 · The paper itself

Abstract

Neuroinflammation occurs in acute and chronic CNS injury, including stroke, traumatic brain injury, and neurodegenerative diseases. Microglia are specialized resident myeloid cells that mediate CNS innate immune responses. Disease-relevant stimuli, such as reactive oxygen species (ROS), can influence microglia activation. Previously, we observed that p53, a ROS-responsive transcription factor, modulates microglia behaviors in vitro and in vivo, promoting proinflammatory functions and suppressing downregulation of the inflammatory response and tissue repair. In this article we describe a novel mechanism by which p53 modulates the functional differentiation of microglia both in vitro and in vivo. Adult microglia from p53-deficient mice have increased expression of the anti-inflammatory transcription factor c-Maf. To determine how p53 negatively regulates c-Maf, we examined the impact of p53 on known c-Maf regulators. MiR-155 is a microRNA that targets c-Maf. We observed that cytokine-induced expression of miR-155 was suppressed in p53-deficient microglia. Furthermore, Twist2, a transcriptional activator of c-Maf, is increased in p53-deficient microglia. We identified recognition sites in the 3' untranslated region of Twist2 mRNA that are predicted to interact with two p53-dependent microRNAs: miR-34a and miR-145. In this article, we demonstrate that miR-34a and -145 are regulated by p53 and negatively regulate Twist2 and c-Maf expression in microglia and the RAW macrophage cell line. Taken together, these findings support the hypothesis that p53 activation induced by local ROS or accumulated DNA damage influences microglia functions and that one specific molecular target of p53 in microglia is c-Maf.

Indexed as

AnimalsBrain IschemiaCell LineDisease Models, AnimalGene Expression RegulationHumansMaleMiceMice, KnockoutMicrogliaMicroRNAsModels, BiologicalPhenotypeProto-Oncogene Proteins c-mafRepressor ProteinsTumor Suppressor Protein p53MicroRNAsMirn155 microRNA, mouseProto-Oncogene Proteins c-mafRepressor ProteinsTumor Suppressor Protein p53Twist2 protein, mouseTwist-Related Protein 1

Identifiers

PMID24319262
PMCPMC4195583
OpenAlexW1858233563

What OpenQuestion holds

Textmetadata
LicenceTDM
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.