Evidence map›Paper›PMID 22675511›Full record

ArticlePloS one2012

Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4α and C/EBPα.

Huma Safdar, Ka Lei Cheung, Hans L Vos, Frank J Gonzalez, Pieter H Reitsma, Yusuke Inoue, Bart J M van Vlijmen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  2. Article
  3. Significance of CCNs in liver regeneration.Journal of cell communication and signaling · 2023
    Review
  4. Article
  5. Article
  6. Review
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  8. Article
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  11. The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2018
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  17. Article
  18. 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

7 authors at 3 institutions in 3 countries.

Huma SafdarEinthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands. h.safdar@lumc.nl
Ka Lei Cheung
Hans L Vos
Frank J Gonzalez
Pieter H Reitsma
Yusuke Inoue
Bart J M van Vlijmen
Leiden University Medical Center · NLGunma University · JPNational Cancer Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocyte nuclear factor 4α (HNF4α) and CCAAT/enhancer-binding protein α (C/EBPα) are important for the transcriptional control of coagulation factors. To determine in vivo the direct role of HNF4α and C/EBPα in control of genes encoding coagulation factors, a synthetic small interfering (si)RNA approach was used that enabled strong reduction of mouse hepatic HNF4α and C/EBPα under conditions that minimized target-related secondary effects. For both HNF4α and C/EBPα, intravenous injection of specific synthetic siRNAs (siHNF4α and siC/EBPα) resulted in more than 75% reduction in their liver transcript and protein levels 2 days post-injection. For siHNF4α, this coincided with marked and significantly reduced transcript levels of the coagulation genes Hrg, Proz, Serpina5, F11, F12, F13b, Serpinf2, F5, and F9 (in order of magnitude of effect) as compared to levels in control siRNA injected animals. Significant decreases in HNF4α target gene mRNA levels were also observed at 5 days post-siRNA injection, despite a limited level of HNF4α knockdown at this time point. Compared to HNF4α, C/EBPα knockdown had a modest impact on genes encoding coagulation factors. A strong reduction in C/EBPα transcript and protein levels resulted in significantly affected transcript levels of the control genes Pck1 and Fasn and a modest downregulation for coagulation genes Fba, Fbg and F5. F5 and F11 were the sole coagulation genes that were significantly affected upon prolonged (5 day) C/EBPα knockdown. We conclude that in the mouse, HNF4α has a direct and essential regulatory role for multiple hepatic coagulation genes, while a role for C/EBPα is more restricted. In addition, this study demonstrates that synthetic siRNA provides a simple and fast means for determining liver transcription factor involvement in vivo.

Indexed as

Gene TargetingGene Transfer TechniquesTranscription, GeneticAnimalsBlood CoagulationCCAAT-Enhancer-Binding ProteinsCells, CulturedFemaleGene Expression RegulationGene Knockdown TechniquesHepatocyte Nuclear Factor 4HepatocytesLiverMiceMice, Inbred C57BLOrgan SpecificityCCAAT-Enhancer-Binding ProteinsCEBPA protein, mouseHepatocyte Nuclear Factor 4Hnf4a protein, mouseRNA, MessengerRNA, Small Interfering

Identifiers

PMID22675511
PMCPMC3365905
OpenAlexW2010077732

What OpenQuestion holds

Textmetadata
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.