Evidence map›Paper›PMID 26057378›Full record

ArticlePloS one2015

Mechanisms of Hypoxic Up-Regulation of Versican Gene Expression in Macrophages.

Fattah Sotoodehnejadnematalahi, Karl J Staples, Elvina Chrysanthou, Helen Pearson, Loems Ziegler-Heitbrock, Bernard Burke

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma.International journal of biological sciences · 2026
    Article
  2. Article
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  4. Article
  5. Article
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  7. Article
  8. A role for proteoglycans in vascular disease.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Review
  9. Provisional matrix: A role for versican and hyaluronan.Matrix biology : journal of the International Society for Matrix Biology · 2017
    Review
  10. 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

6 authors at 5 institutions in 3 countries.

Fattah SotoodehnejadnematalahiDepartment of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Karl J StaplesClinical & Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Southampton, United Kingdom.
Elvina ChrysanthouDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
Helen PearsonDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
Loems Ziegler-HeitbrockEvA Study Center, Asklepios Fachkliniken and Helmholtz-Zentrum Muenchen, Gauting, Germany.
Bernard BurkeDental School, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
University of Leicester · GBAsklepios Fachkliniken München-Gauting · DEBirmingham Dental Hospital · GBIslamic Azad University, Science and Research Branch · IRSouthampton General Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM), and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold) by long term hypoxia (5 days) than by 1 day of hypoxia (48 fold). We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K), LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression.

Indexed as

Base Sequencebeta CateninCell HypoxiaCells, CulturedFlow CytometryHumansHypoxia-Inducible Factor 1, alpha SubunitImmunoblottingLuciferasesMacrophagesMolecular Sequence DataMonocytesPhosphatidylinositol 3-KinasesPromoter Regions, GeneticReal-Time Polymerase Chain ReactionRNA, Messengerbeta CateninHypoxia-Inducible Factor 1, alpha SubunitLuciferasesPhosphatidylinositol 3-KinasesRNA, MessengerVersicans

Identifiers

PMID26057378
PMCPMC4461269
OpenAlexW774424220

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.