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

Tubulin alpha 8 is expressed in hepatic stellate cells and is induced in transformed hepatocytes
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微管蛋白 α 8 在肝星状细胞中表达,并在转化的肝细胞中被诱导

DOI:
10.1007/s11010-016-2926-4
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发表时间:
2017
影响因子:
4.3
通讯作者:
Buechler C
Buechler C
中科院分区:
生物学3区
文献类型:
--
作者:
Rein-Fischboeck L;Pohl R;Haberl EM;Zimny S;Neumann M;Eisinger K;Weiss TS;Krautbauer S;Buechler C

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微管蛋白α 8(TUBA 8)在鼠肝肿瘤中高度丰富,表明在肝细胞癌(HCC)中的作用。非酒精性脂肪性肝炎(NASH)是HCC的危险因素。在用蛋氨酸-胆碱缺乏饮食喂养两周以诱导晚期鼠NASH的小鼠中,我们确实看到TUBA 8蛋白的肝脏水平增加。在给予高脂肪饮食14周或致动脉粥样硬化饮食12周的动物中,肝脏TUBA 8没有变化。TUBA 8在人肝星状细胞(HSC)中高度表达,并与HSC标志物结蛋白共定位于鼠肝脏中。当刺激24小时时,炎症介质(TNF、LPS、IL-6)和促纤维化介质(TGF-β)不调节HepG 2细胞、原代HSC和HSC细胞系LX-2中的TUBA 8。法尼酯X受体和过氧化物酶体增殖物激活受体γ的激动剂是NASH和HCC病理生理学中涉及的核受体,它们对HepG 2和LX-2细胞中的TUBA 8没有影响。在18名患者的人HCC组织中,与相应的非肿瘤组织相比,TUBA 8显著上调。与未转化的肝细胞相比,TUBA 8蛋白在转化细胞中强烈表达。因此,TUBA 8是HSC的标志物,其细胞数量在NASH中增加,而HCC中的较高水平可能与实质细胞中TUBA 8的诱导有关。
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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