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Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models.

ABSTRACT: Emerging evidence has suggested that aberrant expression of micro (mi)RNAs contributes to the development of alcoholic liver injury (ALD). However, miRNA profiles distinguishing different stages of ALD have not yet been reported. The present study was designed to investigate the unique miRNA expression patterns at different stages of ALD in a rat model and analyze the gene functions and pathways of dysregulated miRNA?targeted genes. Using microarray and stem?loop quantitative polymerase chain reaction analyses, 16 miRNAs were identified as upregulated and 13 were identified as downregulated in an alcoholic steatohepatitis (ASH) group compared with the control group, while five miRNAs were identified to be upregulated and eight were identified to be downregulated in the alcoholic fatty liver (AFL) group as compared with the control group. Following further confirmation by Significance Analysis of Microarray and prediction by Prediction Analysis of Microarray, 8 and 12 types of miRNA were screened as molecular signatures in distinguishing AFL and ASH, respectively, from normal rat liver. In addition, several miRNA?target pairs were predicted by computer?aided algorithms (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery platform) and these genes may be involved in cancer signaling pathways, the Wnt signaling pathway and other signaling pathways. These results may provide novel miRNA targets for diagnosis and therapeutic intervention at different stages of ALD.

SUBMITTER: Chen YP

PROVIDER: S-EPMC4121398 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models.

Chen Yi-Peng YP Jin Xi X Kong Mei M Li You-Ming YM

Molecular medicine reports 20140707 3

Emerging evidence has suggested that aberrant expression of micro (mi)RNAs contributes to the development of alcoholic liver injury (ALD). However, miRNA profiles distinguishing different stages of ALD have not yet been reported. The present study was designed to investigate the unique miRNA expression patterns at different stages of ALD in a rat model and analyze the gene functions and pathways of dysregulated miRNA‑targeted genes. Using microarray and stem‑loop quantitative polymerase chain re ...[more]

PMID: 25017766

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Project description:BackgroundRecent reports have shown that microRNAs (miRNAs) regulate vital immunological processes and have emerged as key regulators of immune system development and function. Therefore, it is important to determine miRNA dysregulation and its pathogenic contribution in autoimmune diseases, an aspect not adequately addressed thus far.Methodology/principal findingsIn this study, we profiled miRNA expressions in splenic lymphocytes from three murine lupus models (MRL-lpr, B6-lpr and NZB/W(F₁)) with different genetic background by miRNA microarray assays and Real-time RT-PCR. Despite the genetic differences among these three lupus stains, a common set of dysregulated miRNAs (miR-182-96-183 cluster, miR-31, and miR-155) was identified in splenocytes when compared with age-matched control mice. The association of these miRNAs with the disease was highlighted by our observation that this miRNA expression pattern was evident in NZB/W mice only at an age when lupus disease is manifested. Further, we have shown that the miRNA dysregulation in MRL-lpr mice was not simply due to the activation of splenocytes. By Real-time RT-PCR, we confirmed that these miRNAs were upregulated in both purified splenic B and T cells from MRL-lpr mice. miR-127 and miR-379, which were greatly upregulated in splenocytes from lpr mice, were moderately increased in diseased NZB/W mice. In addition, Real-time RT-PCR revealed that miR-146a, miR-101a, and miR-17-92 were also markedly upregulated in splenic T, but not B cells from MRL-lpr mice.Conclusions/significanceThe identification of common lupus disease-associated miRNAs now forms the basis for the further investigation of the pathogenic contribution of these miRNAs in autoimmune lupus, which will advance our knowledge of the role of miRNAs in autoimmunity. Given that miRNAs are conserved, with regard to both evolution and function, our observation of a common lupus disease-associated miRNA expression pattern in murine lupus models is likely to have significant pathogenic, diagnostic, and/or therapeutic implications in human lupus.

Dataset Information

Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models.

Publications

Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models.

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