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MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.

Abstract：

: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 downregulated, 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.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

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

doi

10.3892/ijmm.2015.2092

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

877-84

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

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MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.