2011 Fiscal Year Final Research Report
Intrahepatic microRNA expression and response to peginterferon-α and ribavirin therapy in patients with chronic hepatitis C
| Project/Area Number |
21590856
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka City University |
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Principal Investigator |
ENOMOTO Masaru 大阪市立大学, 大学院・医学研究科, 准教授 (20423874)
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| Co-Investigator(Kenkyū-buntansha) |
KAWADA Norifumi 大阪市立大学, 大学院・医学研究科, 教授 (30271191)
TAMORI Akihiro 大阪市立大学, 大学院・医学研究科, 准教授 (30291595)
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| Project Period (FY) |
2009 – 2011
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| Keywords | C型慢性肝炎 / マイクロRNA / インターフェロン / リバビリン |
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| Research Abstract |
The regulated microRNAs(miRNAs) in human livers infected with hepatitis C virus(HCV) were identified by microarray analysis. MiR-422a was down-regulated, and miR-199a-5p/199a-3p and miR-221/222 up-regulated in the human liver in a fibrosis progression-dependent manner. Their expression was validated by real-time RT-PCR. Among these miRNAs, miR-222 increased in mouse livers from two fibrosis models. The expression of miR-222 was up-regulated in cultured stellate cells LX-2 and increased during the course of culture-dependent activation of mouse primary stellate cells. NF-κB inhibitor significantly suppressed the miR-222 induction that was stimulated in culture by TNF-α or TGF-α. Although over-expression or down-regulation of miR-222 failed to regulate the growth of LX-2 cells, miR-222 bound to the p27^<Kip1> 3'UTR and regulated the expression of the corresponding protein. Transient transfection with miR-222 precursors significantly up-regulated α1(I) collagen and down-regulated MMP-1 mRNA expressions. In conclusion, miR-222 may be new markers for stellate cell activation and liver fibrosis progression.
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[Journal Article] Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus2011
Author(s)
Tamori A, Kioka K, Kurai O, Sakaguchi H, Enomoto M, Fujii H, Kobayashi S, Iwai S, Morikawa H, Yamaguchi S, Kawasaki Y, Oka H, Tanaka Y, Kawada N
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Journal Title
Hepatol Res
Volume: 41
Pages: 1169-77
Peer Reviewed
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