Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses
| العنوان: | Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses |
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| المؤلفون: | Joan, Manils, Heinz, Fischer, Joan, Climent, Eduard, Casas, Celia, García-Martínez, Jordi, Bas, Supawadee, Sukseree, Tanya, Vavouri, Francisco, Ciruela, Josep Maria, de Anta, Erwin, Tschachler, Leopold, Eckhart, Concepció, Soler |
| المساهمون: | Universitat de Barcelona |
| المصدر: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona Scientific Reports r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| بيانات النشر: | Nature Publishing Group |
| مصطلحات موضوعية: | Keratinocytes, Cell death, Deoxyribonucleases, lcsh:R, ADN, lcsh:Medicine, DNA Fragmentation, DNA, Article, Cell Line, Mice, Inbred C57BL, Skin diseases, Exodeoxyribonucleases, Malalties de la pell, Mort cel·lular, Animals, Humans, lcsh:Q, lcsh:Science, Cells, Cultured, Gene Deletion |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::cdd3038d84c7539711d5c5f4ecd17ebdTest http://hdl.handle.net/2445/122443Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....cdd3038d84c7539711d5c5f4ecd17ebd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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