Evidence map›Paper›PMID 22479529›Full record

ArticlePloS one2012

Silencing of renal DNaseI in murine lupus nephritis imposes exposure of large chromatin fragments and activation of Toll like receptors and the Clec4e.

Dhivya Thiyagarajan, Silje Fismen, Natalya Seredkina, Søren Jacobsen, Thomas Elung-Jensen, Anne-Lise Kamper, Christopher Graham Fenton, Ole Petter Rekvig, Elin Synnøve Mortensen

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 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Frontiers in immunology · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. The Role of NLRP3 Inflammasome in Lupus Nephritis.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Epigenetics and Systemic Lupus Erythematosus: Unmet Needs.Clinical reviews in allergy & immunology · 2016
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
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

9 authors at 2 institutions in 2 countries.

Dhivya ThiyagarajanMolecular Pathology Research Group, Faculty of Medicine, University of Tromsø, Tromsø, Norway.
Silje Fismen
Natalya Seredkina
Søren Jacobsen
Thomas Elung-Jensen
Anne-Lise Kamper
Christopher Graham Fenton
Ole Petter Rekvig
Elin Synnøve Mortensen
UiT The Arctic University of Norway · NOCopenhagen University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent studies demonstrate that transformation of mild lupus nephritis into end-stage disease is imposed by silencing of renal DNaseI gene expression in (NZBxNZW)F1 mice. Down-regulation of DNaseI results in reduced chromatin fragmentation, and in deposition of extracellular chromatin-IgG complexes in glomerular basement membranes in individuals that produce IgG anti-chromatin antibodies. The main focus of the present study is to describe the biological consequences of renal DNaseI shut-down and reduced chromatin fragmentation with a particular focus on whether exposed large chromatin fragments activate Toll like receptors and the necrosis-related Clec4e receptor in murine and human lupus nephritis. Furthermore, analyses where performed to determine if matrix metalloproteases are up-regulated as a consequence of chromatin-mediated Toll like receptors/Clec4e stimulation. Mouse and human mRNA expression levels of DNaseI, Toll like receptors 7-9, Clec4e, pro-inflammatory cytokines and MMP2/MMP9 were determined and compared with in situ protein expression profiles and clinical data. We demonstrate that exposure of chromatin significantly up-regulate Toll like receptors and Clec4e in mice, and also but less pronounced in patients with lupus nephritis treated with immunosuppresants. In conclusion, silencing of renal DNaseI gene expression initiates a cascade of inflammatory signals leading to progression of both murine and human lupus nephritis. Principal component analyses biplot of data from murine and human lupus nephrits demonstrate the importance of DNaseI gene shut down for progression of the organ disease.

Indexed as

AnimalsCells, CulturedChromatinCytokinesDeoxyribonuclease IDisease Models, AnimalFemaleGene SilencingHumansInflammationKidneyLectins, C-TypeLupus NephritisMembrane ProteinsMicePrincipal Component AnalysisChromatinCLEC4D protein, humanClecsf8 protein, mouseCytokinesDeoxyribonuclease ILectins, C-TypeMembrane ProteinsReceptors, ImmunologicRNA, MessengerToll-Like Receptors

Identifiers

PMID22479529
PMCPMC3316608
OpenAlexW2053397585

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.