Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.
Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.
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DOI：
10.1038/labinvest.2010.113
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
非酒精性脂肪性肝炎（NASH）中microRNA（miRNA）表达失调的重要性已被越来越多地认识到;然而，miRNA表达改变与NASH病理生理学特征之间的关联以及NASH易感性与miRNA表达改变之间是否存在联系在很大程度上是未知的。在本研究中，雄性近交系C57 BL/6 J和DBA/2 J小鼠喂食脂肪生成甲基缺乏饮食，导致类似于人类NASH的肝损伤，并确定肝脏中miRNA的表达和这些miRNA靶向的蛋白质水平。甲基缺乏饮食的给药引发C57 BL/6 J和DBA/2 J小鼠肝脏中的NASH特异性变化，DBA/2 J小鼠中的幅度更严重。甲基缺陷型DBA/2 J小鼠肝脏中纤维化相关基因的表达程度更高，证明了这一点。NASH的发展伴随着miRNA表达的显著变化，包括miR-29 c、miR-34 a、miR-155和miR-200 b。有趣的是，与C57 BL/6 J小鼠相比，在喂食甲基缺乏饮食的DBA/2 J小鼠的肝脏中，这些miRNA的表达及其靶点（包括Cebp-β、Socs 1、Zeb-1和E-cadherin）的蛋白质水平的变化更明显。这些结果表明，在甲基缺乏诱导的NASH的发展过程中，miRNA表达的改变是一个突出的事件，并强烈表明NASH的严重程度和对NASH的易感性可能由miRNA表达反应的变化决定。更重要的是，我们的数据提供了miRNA表达改变与NASH病理生理学和病理形态学特征之间的机制联系。
The importance of dysregulation of microRNA (miRNA) expression in nonalcoholic steatohepatitis (NASH) has been increasingly recognized; however, the association between altered expression of miRNAs and pathophysiological features of NASH and whether or not there is a connection between susceptibility to NASH and altered expression of miRNAs are largely unknown. In the present study, male inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet that causes liver injury similar to human NASH, and the expression of miRNAs and the level of proteins targeted by these miRNAs in the livers were determined. The administration of the methyl-deficient diet triggered NASH-specific changes in the livers of C57BL/6J and DBA/2J mice with a magnitude being more severe in DBA/2J mice. This was evidenced by a greater extent of expression of fibrosis-related genes in the livers of methyl-deficient DBA/2J mice. The development of NASH was accompanied by prominent changes in the expression of miRNAs, including miR-29c, miR-34a, miR-155, and miR-200b. Interestingly, changes in the expression of these miRNAs and protein levels of their targets, including Cebp-β, Socs 1, Zeb-1, and E-cadherin, in the livers of DBA/2J mice fed a methyl-deficient diet were more pronounced as compared to the C57BL/6J mice. These results demonstrate that alterations in expression of miRNAs are a prominent event during development of NASH induced by methyl deficiency and strongly suggest that severity of NASH and susceptibility to NASH may be determined by variations in miRNA expression response. More importantly, our data provide a mechanistic link between alterations in miRNA expression and pathophysiological and pathomorphological features of NASH.
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影响因子：
25.7
作者：
Pogribny IP;Tryndyak VP;Bagnyukova TV;Melnyk S;Montgomery B;Ross SA;Latendresse JR;Rusyn I;Beland FA
通讯作者：
Beland FA
影响因子：
4.8
作者：
Nakamura, J;La, DK;Swenberg, JA
通讯作者：
Swenberg, JA
DOI：
10.1016/j.mrfmmm.2006.12.006
发表时间：
2007-06-01
影响因子：
2.3
作者：
Pogribny, Igor P.;Tryndyak, Volodymyr P.;Kovalchuk, Olga
通讯作者：
Kovalchuk, Olga
影响因子：
5.3
作者：
Liang, GG;Chan, MF;Jones, PA
通讯作者：
Jones, PA
影响因子：
11.2
作者：
Hurteau, Gregory J.;Carlson, J. Andrew;Brock, Graham J.
通讯作者：
Brock, Graham J.