HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways.
HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways.
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DOI：
10.3390/ijms15033507
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发表时间：
2014-02-26
影响因子：
5.6
通讯作者：
Li CH
中科院分区：
文献类型：
--
作者：
Wang HY;Yang SL;Liang HF;Li CH
越来越多的证据表明，肝卵圆细胞（又称肝祖细胞）在各种肝病的肝再生过程中发挥重要作用。在B型肝炎病毒（HBV）相关的肝细胞癌（HCC）和慢性肝病中已报道卵圆细胞增殖。研究发现，肝细胞癌患者肝卵圆细胞中存在HBV表面和核心抗原的表达，提示HBV感染卵圆细胞可能是人类肝癌发生的一种机制。此外，有证据表明HBV在卵圆细胞培养中增殖。然而，很少有研究已经进行了探讨HBV编码的蛋白在肝卵圆细胞增殖的作用。在此之前，我们成功地将HBV x（HBx）基因（HBV基因组中的四个基因之一）转染到大鼠LE/6卵圆细胞系中。在这项研究中，我们测试是否转染HBx基因可以影响卵圆细胞在体外增殖。我们的研究结果表明，HBx的过度表达促进卵圆细胞的增殖，并增加细胞周期蛋白D1的表达，在mRNA和蛋白质水平进行评估。我们还发现，HBx激活PI-3 K/Akt和MEK/ERK 1/2途径在HBx转染的卵圆细胞。此外，HBx诱导的细胞周期蛋白D1表达和卵圆细胞增殖的增加被MEK抑制剂PD 184352或PI-3 K抑制剂LY 294002完全消除。以上结果表明，HBx具有促进卵圆细胞增殖的作用，其对卵圆细胞增殖和cyclin D1表达的促进作用依赖于激活卵圆细胞的MEK/ERK和PI 3 K/Akt信号通路。
Growing evidence has shown that hepatic oval cells, also named liver progenitor cells, play an important role in the process of liver regeneration in various liver diseases. Oval cell proliferation has been reported in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and chronic liver disease. Studies have found expression of HBV surface and core antigens in oval cells in the livers of patients with HCC, suggesting that HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. In addition, there is evidence of multiplication of HBV in oval cell culture. However, little research has been performed to explore the role of HBV-encoded proteins in the proliferation of hepatic oval cells. Previously, we successfully transfected the HBV x (HBx) gene, one of the four genes in the HBV genome, into a rat LE/6 oval cell line. In this study, we tested whether or not the transfected HBx gene could affect oval cell proliferation in vitro. Our results show that overexpression of HBx promotes the proliferation of oval cells and increases cyclin D1 expression, assessed at both the mRNA and protein levels. We also found that HBx activated the PI-3K/Akt and MEK/ERK1/2 pathways in HBx-transfected oval cells. Furthermore, the HBx-induced increases in cyclin D1 expression and oval cell proliferation were completely abolished by treatment with either MEK inhibitor PD184352 or PI-3K inhibitor LY294002. These results demonstrated that HBx has the ability to promote oval cell proliferation in vitro, and its stimulatory effects on cell proliferation and expression of cyclin D1 depend on the activation of the MEK/ERK and PI3K/Akt signaling pathways in cultured oval cells.
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影响因子：
6.4
作者：
Sun, C;Jin, XL;Xiao, JC
通讯作者：
Xiao, JC
影响因子：
4.8
作者：
Park, Sung Gyoo;Chung, Chan;Jung, Guhung
通讯作者：
Jung, Guhung
影响因子：
13.5
作者：
Brooling, JT;Campbell, JS;Fausto, N
通讯作者：
Fausto, N
影响因子：
44.1
作者：
Shan, Changliang;Xu, Fuqing;Zhang, Xiaodong
通讯作者：
Zhang, Xiaodong
影响因子：
25.7
作者：
Eleazar, JA;Memeo, L;Bhagat, G
通讯作者：
Bhagat, G