Oliver Waidmann, Thomas Pleli, Andreas Weigert, Esther Imelmann, Bianca Kakoschky, Jens Christian Johannes Schmithals, Claudia Döring, Matthias Frank, Thomas Longerich, Verena Köberle, Martin-Leo Hansmann, Bernhard Brüne, Stefan Zeuzem, Albrecht Piiper, Ivan Đikić
- The nuclear factor kappa beta (NFκB) signaling pathway plays an important role in liver homeostasis and cancer development. Tax1-binding protein 1 (Tax1BP1) is a regulator of the NFκB signaling pathway, but its role in the liver and hepatocellular carcinoma (HCC) is presently unknown. Here we investigated the role of Tax1BP1 in liver cells and murine models of HCC and liver fibrosis. We applied the diethylnitrosamine (DEN) model of experimental hepatocarcinogenesis in Tax1BP1+/+ and Tax1BP1−/− mice. The amount and subsets of non-parenchymal liver cells in in Tax1BP1+/+ and Tax1BP1−/− mice were determined and activation of NFκB and stress induced signaling pathways were assessed. Differential expression of mRNA and miRNA was determined. Tax1BP1−/− mice showed increased numbers of inflammatory cells in the liver. Furthermore, a sustained activation of the NFκB signaling pathway was found in hepatocytes as well as increased transcription of proinflammatory cytokines in isolated Kupffer cells from Tax1BP1−/− mice. Several differentially expressed mRNAs and miRNAs in livers of Tax1BP1−/− mice were found, which are regulators of inflammation or are involved in cancer development or progression. Furthermore, Tax1BP1−/− mice developed more HCCs than their Tax1BP1+/+ littermates. We conclude that Tax1BP1 protects from liver cancer development by limiting proinflammatory signaling.
MetadatenAuthor: | Oliver WaidmannORCiDGND, Thomas PleliORCiD, Andreas WeigertORCiDGND, Esther Imelmann, Bianca KakoschkyGND, Jens Christian Johannes SchmithalsGND, Claudia DöringORCiDGND, Matthias FrankGND, Thomas LongerichORCiDGND, Verena KöberleGND, Martin-Leo HansmannGND, Bernhard BrüneORCiD, Stefan ZeuzemORCiDGND, Albrecht PiiperORCiD, Ivan ĐikićORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-761334 |
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DOI: | https://doi.org/10.1038/s41598-020-73387-4 |
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ISSN: | 2045-2322 |
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Parent Title (English): | Scientific reports |
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Publisher: | Macmillan Publishers Limited, part of Springer Nature |
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Place of publication: | [London] |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2020/10/01 |
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Date of first Publication: | 2020/10/01 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/11/23 |
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Tag: | Cancer; Immunology |
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Volume: | 10 |
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Issue: | art. 16264 |
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Article Number: | 16264 |
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Page Number: | 13 |
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First Page: | 1 |
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Last Page: | 13 |
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Note: | Open Access funding enabled and organized by Projekt DEAL. This work was supported by the “Patenschaftsmodell and the Nachwuchswissenschaftler Programm der Goethe-Universität Frankfurt”, Germany and in parts by the Deutsche Forschungsgemeinschaft (DFG), WA 2924/1-1. |
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HeBIS-PPN: | 516755803 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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