MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.
MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.
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在非酒精性脂肪性肝炎的小鼠模型中，二甲双胍治疗后的microRNA谱。
DOI：
10.3892/ijmm.2015.2092
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Masaki T
中科院分区：
文献类型：
--
作者：
Katsura A;Morishita A;Iwama H;Tani J;Sakamoto T;Tatsuta M;Toyota Y;Fujita K;Kato K;Maeda E;Nomura T;Miyoshi H;Yoneyama H;Himoto T;Fujiwara S;Kobara H;Mori H;Niki T;Ono M;Hirashima M;Masaki T
非酒精性脂肪性肝炎（NASH）是慢性肝病最常见的原因之一，被认为是隐源性肝硬化和肝细胞癌的致病因素。微小RNA（miRNA）是一种小型非编码RNA，可负调节信使RNA（mRNA）。最近，研究表明某些miRNAs的异常表达在肝脏疾病中起着关键作用。本研究的目的是评估NASH模型中与二甲双胍治疗相关的miRNA谱的变化。8周龄雄性小鼠单独喂食蛋氨酸和胆碱缺乏（MCD）饲料或与0.08%二甲双胍一起喂食15周。二甲双胍能显著下调血浆转氨酶水平，减轻肝脂肪变性和肝纤维化。与对照组相比，在71个上调的miRNA中，miRNA-376 a、miRNA-127、miRNA-34 a、miRNA-300和miRNA-342- 3 p的表达增强;在60个下调的miRNA中，miRNA-122、miRNA-194、miRNA-101 b和miRNA-705的表达降低。值得注意的是，在喂食MCD的小鼠中，二甲双胍治疗后miRNA谱发生了改变。在用二甲双胍处理的喂食MCD的小鼠中，miRNA-376 a、miRNA-127、miRNA-34 a、miRNA-300和miRNA-342- 3 p下调，但miRNA-122、miRNA-194、miRNA-101 b和miRNA-705显著上调。在喂食MCD的小鼠中，miRNA谱发生了改变，二甲双胍减弱了这种对miRNA表达的影响。因此，miRNA谱是一个潜在的工具，可用于阐明二甲双胍诱导的肝脂肪变性和肝纤维化改善背后的机制。此外，可靶向的miRNA的鉴定可用作人NASH的新疗法。
Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. microRNAs (miRNAs) are small non-coding RNAs that negatively regulate messenger RNA (mRNA). Recently, it was demonstrated that the aberrant expression of certain miRNAs plays a pivotal role in liver disease. The aim of the present study was to evaluate changes in miRNA profiles associated with metformin treatment in a NASH model. Eight-week-old male mice were fed a methionine- and choline-deficient (MCD) diet alone or with 0.08% metformin for 15 weeks. Metformin significantly downregulated the level of plasma transaminases and attenuated hepatic steatosis and liver fibrosis. The expression of miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p was enhanced among the 71 upregulated miRNAs, and the expression of miRNA-122, miRNA-194, miRNA-101b and miRNA-705 was decreased among 60 downregulated miRNAs in the liver of MCD-fed mice when compared with control mice. Of note, miRNA profiles were altered following treatment with metformin in MCD-fed mice. miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p were down-regulated, but miRNA-122, miRNA-194, miRNA-101b and miRNA-705 were significantly upregulated in MCD-fed mice treated with metformin. miRNA profiles were altered in MCD-fed mice and metformin attenuated this effect on miRNA expression. Therefore, miRNA profiles are a potential tool that may be utilized to clarify the mechanism behind the metformin-induced improvement of hepatic steatosis and liver fibrosis. Furthermore, identification of targetable miRNAs may be used as a novel therapy in human NASH.
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影响因子：
13.5
作者：
Wang, Bo;Majumder, Sarmila;Nuovo, Gerard;Kutay, Huban;Volinia, Stefano;Patel, Tushar;Schmittgen, Thomas D.;Croce, Carlo;Ghoshal, Kalpana;Jacob, Samson T.
通讯作者：
Jacob, Samson T.
影响因子：
3.7
作者：
Pan C;Chen H;Wang L;Yang S;Fu H;Zheng Y;Miao M;Jiao B
通讯作者：
Jiao B
影响因子：
3.7
作者：
Kita Y;Takamura T;Misu H;Ota T;Kurita S;Takeshita Y;Uno M;Matsuzawa-Nagata N;Kato K;Ando H;Fujimura A;Hayashi K;Kimura T;Ni Y;Otoda T;Miyamoto K;Zen Y;Nakanuma Y;Kaneko S
通讯作者：
Kaneko S
影响因子：
2.7
作者：
Chiang, Yeunpo;Song, Yongxi;Xu, Huimian
通讯作者：
Xu, Huimian
影响因子：
4.7
作者：
Khella, H. W. Z.;Bakhet, M.;Yousef, G. M.
通讯作者：
Yousef, G. M.