title: Tubulin alpha 8 is expressed in hepatic stellate cells and is induced in transformed hepatocytes.
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.
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rein-Fischboeck
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Pohl
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Haberl
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zimny
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Neumann
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.affiliation: University Children Hospital (KUNO), Regensburg University Hospital, Regensburg, Germany.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Krautbauer
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany. christa.buechler@klinik.uni-regensburg.de.
authors.forename: Christa
authors.identifier: http://orcid.org/0000-0002-5635-3994
authors.initials: C
authors.lastname: Buechler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002794:Choline / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000009:adverse effects; D051379:Mice; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D014404:Tubulin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C408046:TUBA8 protein, human; C501978:Tuba8 protein, mouse; D014404:Tubulin; D008715:Methionine; D002794:Choline
keywords: Fatty liver; Hepatocellular carcinoma; Inflammation; Liver fibrosis