Induction of microRNA-214-5p in human and rodent liver fibrosis
1 Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno, Osaka 545-8585, Japan
2 Center for the Advancement of Higher Education, Faculty of Engineering, Kinki University, 1, Takaya Umenobe, Higashi-Hiroshima City, Hiroshima 739-2116, Japan
3 PhoenixBio Co. Ltd., Hiroshima, Japan, 3-4-1, Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-0046, Japan
4 Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno, Osaka 545-8585, Japan
Fibrogenesis & Tissue Repair 2012, 5:12 doi:10.1186/1755-1536-5-12Published: 1 August 2012
miRNAs are non-coding RNAs that regulate gene expression in a wide range of biological contexts, including a variety of diseases. The present study clarified the role of miR-214-5p in hepatic fibrogenesis using human clinical tissue samples, livers from rodent models, and cultured hepatic stellate cells.
The expression of miR-214-5p and genes that are involved in liver fibrosis were analyzed in hepatitis C virus-infected human livers, rodent fibrotic livers, a human stellate cell line (LX-2), and the cells from intact mouse livers using real-time PCR. The effect of miR-214-5p overexpression in LX-2 cells on cell function was investigated. Twist-1 expression in the liver tissues of mouse models and primary-cultured stellate cells was also analyzed.
miR-214-5p was upregulated in human and mouse livers in a fibrosis progression–dependent manner. miR-214-5p expression increased during the culture-dependent activation of mouse primary stellate cells and was significantly higher in stellate cells than in hepatocytes. The overexpression of miR-214-5p in LX-2 cells increased the expression of fibrosis-related genes, such as matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin, and transforming growth factor (TGF)-β1. TGF-β stimulation induced miR-214-5p in LX-2 cells. Twist-1 was increased in fibrotic mouse livers and induced during mouse stellate cell activation.
miR-214-5p may play crucial roles in the activation of stellate cells and the progression of liver fibrosis. Twist-1 may regulate miR-214-5p expression in the liver, particularly in stellate cells.