The expression profile and roles of microRNA in tumor necrosis factor α-mediated acute liver failure in mouse model
10.3760/cma.j.issn.1000-6680.2010.12.001
- VernacularTitle:微小RNA在肿瘤坏死因子α介导的急性肝功能衰竭小鼠体内的表达谱及其作用
- Author:
Fangmei AN
;
Dongshan YU
;
Bangdong GONG
;
Gangde ZHAO
;
Hui WANG
;
Qing GUO
;
Hong YU
;
Qing XIE
- Publication Type:Journal Article
- Keywords:
Oligonucleotide array sequence analysis;
microRNAs;
Mice;
Liver failure,acute;
Tumor necrosis factor-alpha
- From:
Chinese Journal of Infectious Diseases
2010;28(12):705-711
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the expression profile of microRNA (miRNA) and the roles in pathogenesis of acute liver failure in mouse model. Methods Eighty-five BALB/c mice were divided into four groups: 40 in model group of acute liver failure were intraperitoneally injected with Dgalactosamine (D-GalN) and lipopolysaccharides (LPS); 20 in D-GalN group were injected with DGalN only; 20 in LPS group were injected with LPS only; 5 in control group were injected with saline.Liver histology of mouse was observed at hour 0, 5, 7 of injection, and sera and liver tissues were collected at hour 0, 1, 3, 5, 7, 9 of injection. Meanwhile, levels of inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in serum and liver tissue were detected by realtime polymerase chain reaction (PCR). Lock nucleic acid (LNA)-based miRNA microarray technology was used to detect the expression profile of hepatic miRNA, and the expression of miRNA was verified by real time quantification-polymerase chain reaction (RT-PCR). Mouse macrophage Raw264.7 cells were induced by LPS in vitro and the expressions of miRNA at different time points were detected.The comparison of means among groups was analyzed using one way ANOVA and the correlation were analyzed by Pearson and Spearman correlation. Results Microarray analysis found that the expression profile of miRNA during the acute liver failure changed dramatically. There were 97 miRNA in model group changed significantly compared with control group (P＜0.01), including 21 up-regulated and 27down-regulated at hour 5 and 7 of injection. Furthermore, the expressions of miR 146a and miR-155were verified by RT-PCR and found they both increased progressively over time after injection.Correlation analysis showed that miR-155 was well correlated with both TNF-α and IL-6 expressions.It was further found that miR-146a and miR-155 were both up-regulated in activated Raw264.7 cells in vitro. Conclusions The expression profile of miRNA changes during acute liver failure in mouse model. Inflammation associated-miR-146a and miR-155 are both up-regulated significantly, which indicatcs that they may play an important regulatory role in pathogenesis of acute liver failurc.
