Abstract
MicroRNAs (miRNAs) are small RNA molecules that function to modulate the expression of target genes, playing important roles in a wide range of physiological and pathological processes. The miRNAs in body fluids have received considerable attention as potential biomarkers of various diseases. In this study, we compared the changes of the plasma miRNA expressions by acute liver injury (hepatocellular injury or cholestasis) and chronic liver injury (steatosis, steatohepatitis and fibrosis) using rat models made by the administration of chemicals or special diets. Using miRNA array analysis, we found that the levels of a large number of miRNAs (121–317 miRNAs) were increased over 2-fold and the levels of a small number of miRNAs (6–35 miRNAs) were decreased below 0.5-fold in all models except in a model of cholestasis caused by bile duct ligation. Interestingly, the expression profiles were different between the models, and the hierarchical clustering analysis discriminated between the acute and chronic liver injuries. In addition, miRNAs whose expressions were typically changed in each type of liver injury could be specified. It is notable that, in acute liver injury models, the plasma level of miR-122, the most abundant miRNA in the liver, was more quickly and dramatically increased than the plasma aminotransferase level, reflecting the extent of hepatocellular injury. This study demonstrated that the plasma miRNA profiles could reflect the types of liver injury (e.g. acute/chronic liver injury or hepatocellular injury/cholestasis/steatosis/steatohepatitis/fibrosis) and identified the miRNAs that could be specific and sensitive biomarkers of liver injury.
Highlights
MicroRNAs are a family of short noncoding RNA whose final product is a 22-nucleotide functional RNA molecule [1]
We considered that the steatosis and steatohepatitis models were established
We found that 16 miRNAs were up-regulated in hepatocellular injury model, 2 miRNAs and 3 miRNAs were down-regulated in cholestasis and steatosis models, respectively (Fig. 4, Table 2)
Summary
MicroRNAs (miRNAs) are a family of short noncoding RNA whose final product is a 22-nucleotide functional RNA molecule [1] They regulate the expression of target genes by binding to complementary regions of transcripts to repress their translation or cause mRNA degradation. It was reported that miRNAs are present in the body fluids such as plasma [6], serum [6], urine [7], and saliva [8,9]. Their expression patterns significantly vary in various diseases suggesting their potential as biomarkers [6,10,11]. Information on the plasma miRNA changes by liver injury is still limited
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