Evidence map›Paper›PMID 28928425›Full record

ArticleScientific reports2017

Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses.

Joan Manils, Heinz Fischer, Joan Climent, Eduard Casas, Celia García-Martínez, Jordi Bas, Supawadee Sukseree, Tanya Vavouri, Francisco Ciruela, Josep Maria de Anta and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

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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

13 authors at 7 institutions in 3 countries.

Joan ManilsDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID 0000-0001-8429-1295
Heinz FischerResearch Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Joan ClimentDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Eduard CasasProgram of Predictive and Personalized Medicine of Cancer (PMPPC) - Institute Germans Trias i Pujol (IGTP), Badalona, Barcelona, Spain.
Celia García-MartínezDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Jordi BasDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Supawadee SuksereeResearch Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Tanya VavouriProgram of Predictive and Personalized Medicine of Cancer (PMPPC) - Institute Germans Trias i Pujol (IGTP), Badalona, Barcelona, Spain.ORCID 0000-0003-2352-9049
Francisco CiruelaDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Josep Maria de AntaDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Erwin TschachlerResearch Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Leopold EckhartResearch Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria. leopold.eckhart@meduniwien.ac.at.ORCID 0000-0002-5645-2036
Concepció SolerDepartament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. concepciosoler@ub.edu.
Institut d'Investigació Biomédica de Bellvitge · ESMedical University of Vienna · ATBellvitge University Hospital · ESInstitute of Predictive and Personalized Medicine of Cancer · ESJosep Carreras Leukaemia Research Institute · ESThe Francis Crick Institute · GBUniversity of Veterinary Medicine Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cornification of keratinocytes on the surface of skin and oral epithelia is associated with the degradation of nuclear DNA. The endonuclease DNase1L2 and the exonuclease Trex2 are expressed specifically in cornifying keratinocytes. Deletion of DNase1L2 causes retention of nuclear DNA in the tongue epithelium but not in the skin. Here we report that lack of Trex2 results in the accumulation of DNA fragments in the cytoplasm of cornifying lingual keratinocytes and co-deletion of DNase1L2 and Trex2 causes massive accumulation of DNA fragments throughout the cornified layers of the tongue epithelium. By contrast, cornification-associated DNA breakdown was not compromised in the epidermis. Aberrant retention of DNA in the tongue epithelium was associated neither with enhanced expression of DNA-driven response genes, such as Ifnb, Irf7 and Cxcl10, nor with inflammation. Of note, the expression of Tlr9, Aim2 and Tmem173, key DNA sensor genes, was markedly lower in keratinocytes and keratinocyte-built tissues than in macrophages and immune tissues, and DNA-driven response genes were not induced by introduction of DNA in keratinocytes. Altogether, our results indicate that DNase1L2 and Trex2 cooperate in the breakdown and degradation of DNA during cornification of lingual keratinocytes and aberrant DNA retention is tolerated in the oral epithelium.

Indexed as

DNA FragmentationGene DeletionAnimalsCell LineCells, CulturedDeoxyribonucleasesDNAExodeoxyribonucleasesHumansKeratinocytesMice, Inbred C57BLDeoxyribonucleasesDNADnase1l2 protein, miceExodeoxyribonucleasesTrex2 protein, mouse

Identifiers

PMID28928425
PMCPMC5605544
OpenAlexW2756081722

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.