miR-27a and 27b selleck chemical CHIR99021 allowed culture-activated rat HSCs to switch to a more quiescent HSC phenotype, with restored cytoplasmic lipid droplets and decreased cell proliferation [12]. In this study, we aimed to reveal the association between miRNA expression patterns and the progression of liver fibrosis by using a chronic liver inflammation model in mouse. We also sought to identify the miRNA expression profile in chronic hepatitis (CH) C patients according to the degree of liver fibrosis, and to clarify how miRNAs contribute to the progression of liver fibrosis. We observed a characteristic miRNA expression profile common to both human liver biopsy specimens and mouse CCL4 specimens, comprising the key miRNAs which are associated with the liver fibrosis.

This information is expected to uncover the mechanism of liver fibrosis and to provide a clearer biomarker for diagnosis of liver fibrosis as well as to aid in the development of more effective and safer therapeutic strategies for liver fibrosis. Results The expression level of several mouse miRNAs was increased by introducing mouse liver fibrosis In order to identify changes in the miRNA expression profile between advanced liver fibrosis and non-fibrotic liver, we intra-peritoneally administered CCL4 in olive oil or olive oil alone twice a week for 4 weeks and then once a week for the next 4 weeks. Mice were sacrificed at 4, 6, or 8 weeks and then the degree of mouse liver fibrosis was determined by microscopy (Figure S1). miRNA expression analysis was performed from the liver tissue collected at the same time.

Histological examination revealed that the degree of liver fibrosis progressed in mice that received CCL4 relative to mice receiving olive oil alone (Figure 1A). Microarray analysis revealed that in CCL4 mice, the expression level of 11 miRNAs was consistently higher than that in control mice (Figure 1B). Figure 1 The change of liver fibrosis in mouse model. miRNA expression profile in each human liver fibrosis grade We then established human miRNAs expression profile by using 105 fresh-frozen human chronic hepatitis (CH) C liver tissues without a history of anti-viral therapy, classified according to the grade of the liver fibrosis (F0, F1, F2, and F3 referred to METAVIR fibrosis stages)(Figure 2, Table S2). Fibrosis grade F0 was considered to be the negative control because these samples were derived from patients with no finding of liver fibrosis.

In zebrafish, most highly tissue-specific miRNAs are expressed during embryonic development; approximately Drug_discovery 30% of all miRNAs are expressed at a given time point in a given tissue [13]. In mammals, the 20�C30% miRNA call rate has recently been validated [14]. Such analysis revealed that the diversity of miRNA expression level among specimens was small. Therefore, we focused on miRNAs with a fold change in mean expression level greater than 1.5 (p<0.