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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 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.

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Verfasserangaben:Oliver WaidmannORCiDGND, Thomas PleliORCiD, Andreas WeigertORCiDGND, Esther Imelmann, Bianca KakoschkyGND, Jens Christian Johannes SchmithalsGND, Claudia DöringGND, Matthias FrankGND, Thomas LongerichORCiDGND, Verena KöberleGND, Martin-Leo HansmannGND, Bernhard BrüneORCiD, Stefan ZeuzemORCiDGND, Albrecht PiiperORCiD, Ivan ĐikićORCiDGND
URN:urn:nbn:de:hebis:30:3-761334
DOI:https://doi.org/10.1038/s41598-020-73387-4
ISSN:2045-2322
Titel des übergeordneten Werkes (Englisch):Scientific reports
Verlag:Macmillan Publishers Limited, part of Springer Nature
Verlagsort:[London]
Dokumentart:Wissenschaftlicher Artikel
Sprache:Englisch
Datum der Veröffentlichung (online):01.10.2020
Datum der Erstveröffentlichung:01.10.2020
Veröffentlichende Institution:Universitätsbibliothek Johann Christian Senckenberg
Datum der Freischaltung:23.11.2023
Freies Schlagwort / Tag:Cancer; Immunology
Jahrgang:10
Ausgabe / Heft:art. 16264
Aufsatznummer:16264
Seitenzahl:13
Erste Seite:1
Letzte Seite:13
Bemerkung:
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.
HeBIS-PPN:516755803
Institute:Medizin
DDC-Klassifikation:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Lizenz (Deutsch):License LogoCreative Commons - CC BY - Namensnennung 4.0 International