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首頁(yè)> 外文OA文獻(xiàn) >Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: An alternative mechanism of HBx-related pathogenesis
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Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: An alternative mechanism of HBx-related pathogenesis

機(jī)譯:乙肝病毒X蛋白(HBx)對(duì)肝細(xì)胞增殖的旁分泌體內(nèi)抑制作用:HBx相關(guān)發(fā)病機(jī)制的另一種機(jī)制

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摘要

The role of the hepatitis B virus X protein (HBx) in the pathogenesis of hepatitis B virus (HBV) infection remains unclear. HBx exhibits pleiotropic biological effects, whose in vivo relevance is a matter for debate. In the present report, we have used a combination of HBx-expressing transgenic mice and liver cell transplantation to investigate the in vivo impact of HBx expression on liver cell proliferation and viability in a regenerative context. We show that moderate HBx expression inhibits liver regeneration after partial hepatectomy in HBx-expressing transgenic mice. We also demonstrate that the transplantation of HBx-expressing liver cells, isolated from HBx transgenic mice, is sufficient to inhibit overall recipient liver regeneration after partial hepatectomy. Moreover, the injection of serum samples drawn from HBx-expressing transgenic mice mimicked the inhibitory effect of HBx on liver regeneration. Finally, the incubation of primary rat hepatocytes with the supernatant of HBx-expressing liver cells inhibits cellular DNA synthesis. Taken together, our results demonstrate a paracrine inhibitory effect of HBx on liver cell proliferation and lead us to propose HBV as one of the few viruses implicated in human cancer which act, at least in part, through paracrine biological pathways.
機(jī)譯:乙型肝炎病毒X蛋白(HBx)在乙型肝炎病毒(HBV)感染的發(fā)病機(jī)理中的作用尚不清楚。 HBx表現(xiàn)出多效性生物學(xué)效應(yīng),其體內(nèi)相關(guān)性尚有爭(zhēng)議。在本報(bào)告中,我們結(jié)合使用了表達(dá)HBx的轉(zhuǎn)基因小鼠和肝細(xì)胞移植,以研究HBx表達(dá)在再生環(huán)境下對(duì)肝細(xì)胞增殖和生存力的體內(nèi)影響。我們顯示中度HBx表達(dá)抑制表達(dá)HBx的轉(zhuǎn)基因小鼠部分肝切除后的肝再生。我們還證明,從HBx轉(zhuǎn)基因小鼠中分離出的表達(dá)HBx的肝細(xì)胞的移植足以抑制部分肝切除術(shù)后總體受體肝臟的再生。此外,從表達(dá)HBx的轉(zhuǎn)基因小鼠抽取的血清樣品的注射模仿了HBx對(duì)肝臟再生的抑制作用。最后,將原代大鼠肝細(xì)胞與表達(dá)HBx的肝細(xì)胞上清液一起孵育會(huì)抑制細(xì)胞DNA的合成。綜上所述,我們的結(jié)果證明了HBx對(duì)肝細(xì)胞增殖的旁分泌抑制作用,并促使我們提出HBV是與人類癌癥有關(guān)的為數(shù)不多的至少部分通過(guò)旁分泌生物學(xué)途徑起作用的病毒之一。

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