The Progression of Liver Fibrosis Is Related with Overexpression of the miR-199 and 200 Families

• Published in: PloS one Vol. 6; no. 1; p. e16081
• Main Authors: Murakami, Yoshiki, Toyoda, Hidenori, Tanaka, Masami, Kuroda, Masahiko, Harada, Yoshinori, Matsuda, Fumihiko, Tajima, Atsushi, Kosaka, Nobuyoshi, Ochiya, Takahiro, Shimotohno, Kunitada
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.01.2011; Public Library of Science (PLoS)
• Subjects: Aberration; Animals; Antiviral agents; Bile; Biological activity; Biology; Biopsy; Carbon tetrachloride; Cirrhosis; Comparative analysis; Correlation; Development and progression; Diagnostic software; Diagnostic systems; Disease Progression; Fats and oils; Fibrosis; Gene Expression; Gene Expression Regulation; Genes; Hepatic Stellate Cells - pathology; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatocellular carcinoma; Humans; Interferon; Kinases; Liver; Liver cancer; Liver cirrhosis; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; Medicine; Mice; MicroRNA; MicroRNAs - analysis; miRNA; Molecular modelling; Oils & fats; Olive oil; Quality; RNA, Neoplasm - analysis; Rodents; Severity of Illness Index; Stellate cells; Therapeutic applications; Up-Regulation; Viral infections; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0016081

Chronic hepatitis C (CH) can develop into liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Liver fibrosis and HCC development are strongly correlated, but there is no effective treatment against fibrosis because the critical mechanism of progression of liver fibrosis is not fully understood. microRNAs (miRNAs) are now essential to the molecular mechanisms of several biological processes. In order to clarify how the aberrant expression of miRNAs participates in development of the liver fibrosis, we analyzed the liver fibrosis in mouse liver fibrosis model and human clinical samples. In a CCL(4)-induced mouse liver fibrosis model, we compared the miRNA expression profile from CCL(4) and olive oil administrated liver specimens on 4, 6, and 8 weeks. We also measured expression profiles of human miRNAs in the liver biopsy specimens from 105 CH type C patients without a history of anti-viral therapy. Eleven mouse miRNAs were significantly elevated in progressed liver fibrosis relative to control. By using a large amount of human material in CH analysis, we determined the miRNA expression pattern according to the grade of liver fibrosis. We detected several human miRNAs whose expression levels were correlated with the degree of progression of liver fibrosis. In both the mouse and human studies, the expression levels of miR-199a, 199a*, 200a, and 200b were positively and significantly correlated to the progressed liver fibrosis. The expression level of fibrosis related genes in hepatic stellate cells (HSC), were significantly increased by overexpression of these miRNAs. Four miRNAs are tightly related to the grade of liver fibrosis in both human and mouse was shown. This information may uncover the critical mechanism of progression of liver fibrosis. miRNA expression profiling has potential for diagnostic and therapeutic applications.