Web of Science: 4 citations, Scopus: 4 citations, Google Scholar: citations
Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses
Manils, Joan (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Fischer, Heinz (Medical University of Vienna. Department of Dermatology)
Climent, Joan (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Casas, Eduard (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
García-Martínez, Celia (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Bas, Jordi (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Sukseree, Supawadee (Medical University of Vienna. Department of Dermatology)
Vavouri, Tanya (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Ciruela, Francisco (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
de Anta, Josep Maria (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Tschachler, Erwin (Medical University of Vienna. Department of Dermatology)
Eckhart, Leopold (Medical University of Vienna. Department of Dermatology)
Soler, Concepció (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Universitat Autònoma de Barcelona

Date: 2017
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.
Note: Número d'acord de subvenció MINECO/BFU2010-15674
Note: Número d'acord de subvenció MINECO/BFU2015-70581
Note: Número d'acord de subvenció MINECO/SAF2014-55700
Note: Altres ajuts: Universitat de Barcelona (ACESB14) i AGAUR
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Published in: Scientifics reports, Vol. 7 (september 2017) , p. 1-12

DOI: 10.1038/s41598-017-12308-4
PMID: 28928425


12 p, 3.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-10-24, last modified 2019-07-17



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