Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis

Abstract 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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/740d319af09b47b9b936f1021dead416
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spelling	oai:doaj.org-article:740d319af09b47b9b936f1021dead4162021-12-02T18:51:28ZTax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis10.1038/s41598-020-73387-42045-2322https://doaj.org/article/740d319af09b47b9b936f1021dead4162020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73387-4https://doaj.org/toc/2045-2322Abstract 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.Oliver WaidmannThomas PleliAndreas WeigertEsther ImelmannBianca KakoschkyChristian SchmithalsClaudia DöringMatthias FrankThomas LongerichVerena KöberleMartin-Leo HansmannBernhard BrüneStefan ZeuzemAlbrecht PiiperIvan DikicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Oliver Waidmann
title	Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
title_short	Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
title_full	Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
title_fullStr	Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
title_full_unstemmed	Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
title_sort	tax1bp1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/740d319af09b47b9b936f1021dead416
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Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis

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