Evidence map›Paper›PMID 22139845›Full record

ArticleThe Journal of biological chemistry2012

The p65 subunit of NF-κB inhibits COL1A1 gene transcription in human dermal and scleroderma fibroblasts through its recruitment on promoter by protein interaction with transcriptional activators (c-Krox, Sp1, and Sp3).

Gallic Beauchef, Nicolas Bigot, Magdalini Kypriotou, Emmanuelle Renard, Benoît Porée, Russell Widom, Anne Dompmartin-Blanchere, Thierry Oddos, François-Xavier Maquart, Magali Demoor and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 59 citations in OpenAlex.

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  8. Deciphering Collagen Phenotype Dynamics Regulators: Insights from In-Silico Analysis.Journal of bioinformatics and systems biology : Open access · 2024
    Article
  9. Reviewing the Regulators of COL1A1.International journal of molecular sciences · 2023
    Review
  10. Article
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  12. Article
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  17. Repression of eEF2K transcription by NF-κB tunes translation elongation to inflammation and dsDNA-sensing.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  18. Article
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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

12 authors at 5 institutions in 2 countries.

Gallic BeauchefLaboratoire Matrice Extracellulaire et Pathologie, IFR ICORE 146, Université de Caen/Basse-Normandie, UFR de Médecine, CHU niveau 3, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
Nicolas Bigot
Magdalini Kypriotou
Emmanuelle Renard
Benoît Porée
Russell Widom
Anne Dompmartin-Blanchere
Thierry Oddos
François-Xavier Maquart
Magali Demoor
Karim Boumediene
Philippe Galera
Université de Caen Normandie · FRBoston University · USCentre National de la Recherche Scientifique · FRHôpital Georges-Clemenceau · FRJohnson & Johnson (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transcriptional mechanisms regulating type I collagen genes expression in physiopathological situations are not completely known. In this study, we have investigated the role of nuclear factor-κB (NF-κB) transcription factor on type I collagen expression in adult normal human (ANF) and scleroderma (SF) fibroblasts. We demonstrated that NF-κB, a master transcription factor playing a major role in immune response/apoptosis, down-regulates COL1A1 expression by a transcriptional control involving the -112/-61 bp sequence. This 51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1) and Sp3, acting as trans-activators of type I collagen expression in ANF and SF. Knockdown of each one of these trans factors by siRNA confirmed the trans-activating effect of Sp1/Sp3 and the p65 subunit of NF-κB trans-inhibiting effect on COL1A1 expression. Despite no existing κB consensus sequence in the COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-κB bind and/or are recruited on the proximal promoter in chromatin immunoprecipitation (ChIP) assays. Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65 are necessary to mediate the NF-κB inhibitory effect on COL1A1 in ANF and SF were carried out; in this regard, immunoprecipitation assays revealed that they interact, and this was validated by re-ChIP. Finally, the knockdown of Sp1/Sp3/c-Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF, suggesting that particular interactions are characteristic of the scleroderma phenotype. In conclusion, our findings highlight a new mechanism for COL1A1 transcriptional regulation by NF-κB, and these data could allow the development of new antifibrotic strategies.

Indexed as

Response ElementsTranscription, GeneticAdultChildChild, PreschoolCollagen Type ICollagen Type I, alpha 1 ChainDermisDNA-Binding ProteinsFibroblastsGene Expression RegulationHumansMaleScleroderma, LocalizedSp1 Transcription FactorSp3 Transcription FactorCollagen Type ICollagen Type I, alpha 1 ChainDNA-Binding ProteinsRELA protein, humanSp1 Transcription FactorSP3 protein, humanSp3 Transcription FactorTranscription Factor RelATranscription FactorsZBTB7B protein, human

Identifiers

PMID22139845
PMCPMC3271000
OpenAlexW1996995915

What OpenQuestion holds

Textmetadata
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.