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

April-2015 Volume 35 Issue 4

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April-2015 Volume 35 Issue 4

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Article Open Access

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
View Affiliations / Copyright

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

Copyright: © Katsura et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 877-884
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Published online on: February 6, 2015

https://doi.org/10.3892/ijmm.2015.2092
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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