title: Micro-RNA profiling in human serum reveals compartment-specific roles of miR-571 and miR-652 in liver cirrhosis.
abstract: OBJECTIVE
  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-β. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.forename: Tobias
authors.initials: T
authors.lastname: Mollnow
authors.forename: Brenda
authors.initials: B
authors.lastname: Bongaerts
authors.forename: Natalia
authors.initials: N
authors.lastname: Elfimova
authors.forename: David
authors.initials: D
authors.lastname: Vargas Cardenas
authors.forename: Katharina
authors.initials: K
authors.lastname: Berger
authors.forename: Henning
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Mihael
authors.initials: M
authors.lastname: Vucur
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000235:genetics; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D042541:Intracellular Space / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C574012:MIRN571 microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs