Roderburg, Christoph and Mollnow, Tobias and Bongaerts, Brenda and Elfimova, Natalia and Cardenas, David Vargas and Berger, Katharina and Zimmermann, Henning and Koch, Alexander and Vucur, Mihael and Luedde, Mark and Hellerbrand, Claus and Odenthal, Margarete and Trautwein, Christian and Tacke, Frank and Luedde, Tom (2012) Micro-RNA Profiling in Human Serum Reveals Compartment-Specific Roles of miR-571 and miR-652 in Liver Cirrhosis. PLOS ONE, 7 (3): e32999. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background and Aims: Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. Methods: We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. Results: The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-beta. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. Conclusion: Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular compartments involved in the pathogenesis of liver cirrhosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STELLATE CELL ACTIVATION; C VIRUS-INFECTION; HEPATOCELLULAR-CARCINOMA; CIRCULATING MICRORNAS; FIBROSIS; EXPRESSION; BIOMARKERS; DISEASE; CANCER; TISSUE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 09:11 |
| Last Modified: | 18 May 2020 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19064 |
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