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Tubulin alpha 8 is expressed in hepatic stellate cells and is induced in transformed hepatocytes

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Abstract

Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver. Inflammatory (TNF, LPS, IL-6) and profibrotic mediators (TGF-beta) do not regulate TUBA8 in HepG2 cells, primary HSC and the HSC cell line LX-2, when stimulated for 24 h. Agonists of the farnesoid X receptor and peroxisome proliferator activated receptor gamma, which are nuclear receptors involved in NASH and HCC pathophysiology, have no effect on TUBA8 in HepG2 and LX-2 cells. In human HCC tissues of 18 patients TUBA8 is significantly upregulated when compared to the corresponding non-tumorous tissues. Compared to non-transformed hepatocytes, TUBA8 protein is strongly expressed in transformed cells. Thus, TUBA8 is a marker of HSC whose cell number is increased in NASH, while higher levels in HCC may be related to induction of TUBA8 in parenchymal cells.

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Acknowledgements

The study was supported by the German Research Foundation (BU 1141/12 − 1) to CB and the German Federal Ministry of Education and Research (Virtual Liver Network Grants 0315753) to TSW. The authors are grateful to Professor Charalampos Aslanidis for helpful suggestions.

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Authors and Affiliations

  1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany

    Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M. Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Sabrina Krautbauer & Christa Buechler

  2. University Children Hospital (KUNO), Regensburg University Hospital, Regensburg, Germany

    Thomas S. Weiss

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  1. Lisa Rein-Fischboeck
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Correspondence to Christa Buechler.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Experimental procedures complied with the guidelines of the charitable state controlled foundation Human Tissue and Cell Research. The study was approved by the local ethical committee of the University of Regensburg. Written informed patient’s consent was obtained. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Animal studies were authorized by the University of Regensburg Laboratory Animal Committee and complied with the German Law on Animal Protection and the Institute for Laboratory Animal Research Guide for the Care and Use of Laboratory Animals, 1999. Experiments were conducted according to institutional and governmental regulations for animal use (Government of the Oberpfalz).

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Rein-Fischboeck, L., Pohl, R., Haberl, E.M. et al. Tubulin alpha 8 is expressed in hepatic stellate cells and is induced in transformed hepatocytes. Mol Cell Biochem 428, 161–170 (2017). https://doi.org/10.1007/s11010-016-2926-4

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  • DOI: https://doi.org/10.1007/s11010-016-2926-4

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