ONO Masafumi
   Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine
Article types Original article
Language English
Peer review Peer reviewed
Title MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.
Journal Formal name:International journal of molecular medicine
Abbreviation:Int J Mol Med
ISSN code:1791244X/11073756
Domestic / ForeginForegin
Volume, Issue, Page 35(4),pp.877-84
Author and coauthor Katsura Akiko, Morishita Asahiro, Iwama Hisakazu, Tani Joji, Sakamoto Teppei, Tatsuta Miwa, Toyota Yuka, Fujita Koji, Kato Kiyohito, Maeda Emiko, Nomura Takako, Miyoshi Hisaaki, Yoneyama Hirohito, Himoto Takashi, Fujiwara Shintaro, Kobara Hideki, Mori Hirohito, Niki Toshiro, Ono Masafumi, Hirashima Mitsuomi, Masaki Tsutomu
Publication date 2015/04
Summary 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.
DOI 10.3892/ijmm.2015.2092
PMID 25672270