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Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis

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 invest...

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Main Authors: Waidmann, Oliver (Author) , Pleli, Thomas (Author) , Weigert, Andreas (Author) , Imelmann, Esther (Author) , Kakoschky, Bianca (Author) , Schmithals, Jens Christian Johannes (Author) , Döring, Claudia (Author) , Frank, Matthias (Author) , Longerich, Thomas (Author) , Köberle, Verena (Author) , Hansmann, Martin-Leo (Author) , Brüne, Bernhard (Author) , Zeuzem, Stefan (Author) , Piiper, Albrecht (Author) , Đikić, Ivan (Author)
Format: Article (Journal)
Language:English
Published: 01 October 2020
In: Scientific reports
Year: 2020, Volume: 10
ISSN:2045-2322
DOI:10.1038/s41598-020-73387-4
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-020-73387-4
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-020-73387-4
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Author Notes:Oliver Waidmann, Thomas Pleli, Andreas Weigert, Esther Imelmann, Bianca Kakoschky, Christian Schmithals, Claudia Döring, Matthias Frank, Thomas Longerich, Verena Köberle, Martin-Leo Hansmann, Bernhard Brüne, Stefan Zeuzem, Albrecht Piiper & Ivan Dikic
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Summary: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.
Item Description:Gesehen am 04.11.2020
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-020-73387-4

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