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

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

doi:10.3892/ijmm.2015.2092

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

Authors:
- Akiko Katsura
- Asahiro Morishita
- Hisakazu Iwama
- Joji Tani
- Teppei Sakamoto
- Miwa Tatsuta
- Yuka Toyota
- Koji Fujita
- Kiyohito Kato
- Emiko Maeda
- Takako Nomura
- Hisaaki Miyoshi
- Hirohito Yoneyama
- Takashi Himoto
- Shintaro Fujiwara
- Hideki Kobara
- Hirohito Mori
- Toshiro Niki
- Masafumi Ono
- Mitsuomi Hirashima
- Tsutomu Masaki
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Affiliations: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan, Life Science Research Center, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan, Department of Immunology and Immunopathology, Kagawa University School of Medicine, Kita-gun, Kagawa, Department of Gastroenterology and Hepatology, Kochi Medical School, Koichi, Japan
Published online on: February 6, 2015 https://doi.org/10.3892/ijmm.2015.2092
Pages: 877-884
Copyright: © Katsura et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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