Expression profile of lipid metabolism-associated genes in hepatitis C virus-infected human liver
Expression profile of lipid metabolism-associated genes in hepatitis C virus-infected human liver
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DOI：
10.1111/j.1872-034x.2010.00700.x
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发表时间：
2010-09-01
影响因子：
4.2
通讯作者：
Enjoji, Munechika
中科院分区：
文献类型：
--
作者：
Fujino, Tatsuya;Nakamuta, Makoto;Enjoji, Munechika
目的：最近的研究表明，丙型肝炎病毒（HCV）的进入、复制和分泌需要脂质代谢途径。尽管对人类 HCV 的生命周期知之甚少，但胆固醇和脂肪酸生物合成的激活可能对 HCV 增殖至关重要。 方法：我们评估了从慢性丙型肝炎患者获得的肝脏样本中胆固醇和脂肪酸生物合成必需基因的转录水平，并确定了它们的相关性。还测量了血清低密度脂蛋白（LDL）胆固醇和HCV核心抗原的水平。结果：HCV感染的肝脏中LDL受体（LDLR）的基因表达受到抑制，而SREBP1c、肝脏X受体-α（LXRα）、脂肪酸合酶（FASN）、HMG-CoA还原酶和合成酶（HMGR和HMGS）的基因表达显着增加，并且与正常肝脏相比，HCV感染的肝脏中SREBP2的转录相当。在 HCV 感染和对照肝脏中，LDLR 与 HMGR、HMGR 与 SREBP1c 以及 LDLR 与 SREBP2 呈正相关。尽管 LXR α-SREBP1c-FASN 通路上调，但在 HCV 感染的肝脏中，蛋白酶体激活剂 28 γ (PA28 γ) 在转录水平上下调，并且与检查的其他基因没有显着相关。血清LDL胆固醇水平与LDLR和HMGR表达呈负相关。结论：这些结果表明，在HCV感染的肝脏中，胆固醇负荷增加，胆固醇摄取受到控制，而胆固醇从头合成与正常生理状态相比上调。一些胆固醇代谢相关基因表达水平的正相关表明，HCV 感染的肝脏中并非所有代谢途径都失调。
Aim:Recent studies have shown that lipid metabolic pathways are required for the entry, replication and secretion of hepatitis C virus (HCV). Although little is known about the life cycle of HCV in humans, the activation of cholesterol and fatty acid biosynthesis may be critical for HCV proliferation.Methods:We assessed the transcription levels of genes essential for cholesterol and fatty acid biosynthesis in liver samples obtained from patients with chronic hepatitis C and determined their correlations. The serum levels of low-density lipoprotein (LDL) cholesterol and HCV core antigen were also measured.Results:The gene expression of the LDL receptor (LDLR) was suppressed, whereas that of SREBP1c, liver X receptor-alpha (LXR alpha), fatty acid synthase (FASN), and HMG-CoA reductase and synthase (HMGR and HMGS) was significantly increased, and SREBP2 transcription was comparable in HCV-infected liver compared with normal liver. Positive correlations were found for LDLR versus HMGR, HMGR versus SREBP1c, and LDLR versus SREBP2 in the HCV-infected and control liver. Although the LXR alpha-SREBP1c-FASN pathway was upregulated, proteasome activator 28 gamma (PA28 gamma) was downregulated at the transcriptional level in HCV-infected liver, and was not significantly correlated with the other genes examined. The serum LDL cholesterol level was negatively correlated with LDLR and HMGR expression.Conclusion:These results suggest that, in HCV-infected liver, the cholesterol load increases and cholesterol uptake is controlled, while de novo cholesterol synthesis is upregulated compared with the normal physiological state. The positive correlations in the expression levels of some cholesterol metabolism-associated genes indicate that not all of the metabolic pathways are dysregulated in HCV-infected liver.