Aberrant Hepatic MicroRNA Expression in Nonalcoholic Fatty Liver Disease
Aberrant Hepatic MicroRNA Expression in Nonalcoholic Fatty Liver Disease
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非酒精性脂肪性肝病中肝脏 MicroRNA 的异常表达
DOI：
10.1159/000366394
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Fu, Jun Fen
中科院分区：
文献类型：
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作者：
Feng, Yue Ying;Xu, Xiao Qin;Fu, Jun Fen
背景/目的：新出现的证据表明，microRNA（miRNA）介导的基因调控影响代谢稳态的维持，特别是肥胖和胰岛素抵抗的状态，从而提供了miRNA和非酒精性脂肪性肝病（NAFLD）之间的潜在联系。方法：采用高脂饲料喂养SD大鼠，建立非酒精性脂肪肝（NAFLD）模型。使用Illumina HiSeq深度测序评估肝组织的miRNA表达谱。然后在4周和12周的时间点通过实时PCR验证选定的miRNA。此外，在用游离脂肪酸（FFA）和促炎因子（肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6））处理的HepG 2细胞和人肝细胞中评估这些miRNA的表达水平。结果：我们的研究结果表明，食用HFD 4周引起单纯性脂肪变性，在12周时进展为脂肪性肝炎。miRNA深度测序分析鉴定了44种已知上调的miRNA（倍数变化>1.5）和12种下调的miRNA（倍数变化<0.5）。在异常表达的miRNAs中，miR-200 a、miR-200 b、miR-200 c、miR-146 a、miR-146 b和miR-152在体内外均上调。有趣的是，在用FFA和促炎因子处理后，这六种miRNA在HepG 2细胞和人肝细胞中的表达水平增加。结论：miRNAs在NAFLD的发病机制中起重要作用。
Background/Aim: Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). Methods: Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Results: Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change >1.5) and 12 down-regulated miRNAs (fold change <0.5). Among the abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors. Conclusion: These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.