Differential expression of microRNAs in mouse liver under aberrant energy metabolic status
Differential expression of microRNAs in mouse liver under aberrant energy metabolic status
复制标题
能量代谢异常状态下小鼠肝脏中 MicroRNA 的差异表达。
DOI：
10.1194/jlr.m800509-jlr200
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发表时间：
2009-09-01
影响因子：
6.5
通讯作者：
Zhang, Chen-Yu
中科院分区：
文献类型：
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作者：
Li, Shengjie;Chen, Xi;Zhang, Chen-Yu
尽管多年的努力，非酒精性脂肪性肝病（NAFLD）的确切发病机制仍然不清楚。为了深入了解microRNAs（miRNAs）在NAFLD异常能量代谢状态和发病机制中的调控作用，我们利用miRNAs芯片分析了ob/ob小鼠、链脲佐菌素（STZ）诱导的1型糖尿病小鼠和正常C57 BL/6小鼠肝脏中miRNAs的表达。与正常C57 BL/6小鼠相比，ob/ob小鼠脂肪肝中8种miRNAs表达上调，4种miRNAs表达下调。在STZ诱导的糖尿病小鼠的肝脏中发现miR-34 a的上调和miR-122的下调。这些结果表明，不同的miRNA在NAFLD和高血糖症中强烈失调。ob/ob小鼠和STZ给药小鼠肝脏中miRNA表达的比较进一步揭示了ob/ob小鼠肝脏中4种miRNA的上调和2种miRNA的下调，表明这些miRNA可能代表了NAFLD的分子特征。在ob/ob小鼠肝脏中鉴定了独特的miRNA表达模式，并且该模式的分层聚类可以清楚地将ob/ob小鼠与正常C57 BL/6小鼠或STZ施用小鼠区分开。这些发现表明miRNAs在肝脏能量代谢中的重要作用，并暗示miRNAs参与NAFLD的病理生理过程。Li，S.，X. Chen，H. Zhang，X. Liang，Y.湘C. Yu，K. Zen，Y. Li和C-Y。张某能量代谢异常状态下小鼠肝脏microRNAs的差异表达。J. Lipid Res. 2009. 50：1756-1765。
Despite years of effort, exact pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains obscure. To gain an insight into the regulatory roles of microRNAs (miRNAs) in aberrant energy metabolic status and pathogenesis of NAFLD, we analyzed the expression of miRNAs in livers of ob/ob mice, streptozotocin (STZ)-induced type 1 diabetic mice, and normal C57BL/6 mice by miRNA microarray. Compared with normal C57BL/6 mice, ob/ob mice showed upregulation of eight miRNAs and downregulation of four miRNAs in fatty livers. Upregulation of miR-34a and downregulation of miR-122 was found in livers of STZ-induced diabetic mice. These results demonstrate that distinct miRNAs are strongly dysregulated in NAFLD and hyperglycemia. Comparison between miRNA expressions in livers of ob/ob mice and STZ-administered mice further revealed upregulation of four miRNAs and downregulation of two miRNAs in livers of ob/ob mice, indicating that these miRNAs may represent a molecular signature of NAFLD. A distinctive miRNA expression pattern was identified in ob/ob mouse liver, and hierarchical clustering of this pattern could clearly discriminate ob/ob mice from either normal C57BL/6 mice or STZ-administered mice. These findings suggest an important role of miRNAs in hepatic energy metabolism and implicate the participation of miRNAs in the pathophysiological processes of NAFLD.-Li, S., X. Chen, H. Zhang, X. Liang, Y. Xiang, C. Yu, K. Zen, Y. Li, and C-Y. Zhang. Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J. Lipid Res. 2009. 50: 1756-1765.