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

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 - Int. J. Mol. Med. (2015)

Bottom Line: The aim of the present study was to evaluate changes in miRNA profiles associated with metformin treatment in a NASH model.Metformin significantly downregulated the level of plasma transaminases and attenuated hepatic steatosis and liver fibrosis.Furthermore, identification of targetable miRNAs may be used as a novel therapy in human NASH.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.

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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Related in: MedlinePlus

Hierarchical clustering of liver tissues from MCD-fed mice and control group. Liver tissue was clustered according to the expression profiles of 131 differentially expressed miRNAs between the MCD-fed mice and the control group. The analyzed samples are reported in columns and the miRNAs are presented in rows. The miRNA clustering tree is shown on the left, and the sample clustering tree appears at the top. The color scale shown at the top indicates the relative expression level of miRNAs, with red representing a high expression level and blue, a low expression level.
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f4-ijmm-35-04-0877: Hierarchical clustering of liver tissues from MCD-fed mice and control group. Liver tissue was clustered according to the expression profiles of 131 differentially expressed miRNAs between the MCD-fed mice and the control group. The analyzed samples are reported in columns and the miRNAs are presented in rows. The miRNA clustering tree is shown on the left, and the sample clustering tree appears at the top. The color scale shown at the top indicates the relative expression level of miRNAs, with red representing a high expression level and blue, a low expression level.

Mentions: To elucidate the miRNA profiles during the development of NASH, we analyzed the expression levels of 1,135 mouse miRNA probes using liver tissue from control and MCD-fed mice. As shown in Table IA, 71 miRNAs were significantly upregulated, and 60 miRNAs were downregulated in MCD-fed mice. Unsupervised hierarchical clustering analysis using a Pearson’s correlation showed that MCD-fed mice clustered separately from the control group (Fig. 4). These subsets of 131 miRNAs exhibited significant alterations in their expression levels between the MCD-fed and control mice.


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

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 - Int. J. Mol. Med. (2015)

Hierarchical clustering of liver tissues from MCD-fed mice and control group. Liver tissue was clustered according to the expression profiles of 131 differentially expressed miRNAs between the MCD-fed mice and the control group. The analyzed samples are reported in columns and the miRNAs are presented in rows. The miRNA clustering tree is shown on the left, and the sample clustering tree appears at the top. The color scale shown at the top indicates the relative expression level of miRNAs, with red representing a high expression level and blue, a low expression level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356452&req=5

f4-ijmm-35-04-0877: Hierarchical clustering of liver tissues from MCD-fed mice and control group. Liver tissue was clustered according to the expression profiles of 131 differentially expressed miRNAs between the MCD-fed mice and the control group. The analyzed samples are reported in columns and the miRNAs are presented in rows. The miRNA clustering tree is shown on the left, and the sample clustering tree appears at the top. The color scale shown at the top indicates the relative expression level of miRNAs, with red representing a high expression level and blue, a low expression level.
Mentions: To elucidate the miRNA profiles during the development of NASH, we analyzed the expression levels of 1,135 mouse miRNA probes using liver tissue from control and MCD-fed mice. As shown in Table IA, 71 miRNAs were significantly upregulated, and 60 miRNAs were downregulated in MCD-fed mice. Unsupervised hierarchical clustering analysis using a Pearson’s correlation showed that MCD-fed mice clustered separately from the control group (Fig. 4). These subsets of 131 miRNAs exhibited significant alterations in their expression levels between the MCD-fed and control mice.

Bottom Line: The aim of the present study was to evaluate changes in miRNA profiles associated with metformin treatment in a NASH model.Metformin significantly downregulated the level of plasma transaminases and attenuated hepatic steatosis and liver fibrosis.Furthermore, identification of targetable miRNAs may be used as a novel therapy in human NASH.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.

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.

Show MeSH
Related in: MedlinePlus