title: Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases.
abstract: OBJECTIVE
  Serum concentrations of miR-122 were proposed as a marker for various inflammatory diseases, but the mechanisms driving alterations in miR-122 serum levels are unknown.
  
  
  METHODS
  We analysed miR-122 serum levels and hepatic miR-122 expression in mice after hepatic ischaemia and reperfusion (I/R) injury. These data were compared with data from mice after caecal pole ligation and puncture (CLP) procedure. To translate these data into the human, we analysed miR-122 serum concentrations in a cohort of 223 patients with critical illness and 57 patients with cirrhosis.
  
  
  RESULTS
  We detected strongly elevated levels of miR-122 in mice after hepatic I/R injury. miR-122-concentrations correlated with the degree of liver damage according to AST/ALT and were associated with the presence of hepatic cell death detected by TUNEL staining. miR-122 levels were elevated in the cellular supernatants in an in vitro model of hepatocyte injury, supporting the hypothesis that the passive release of miR-122 represents a surrogate for hepatocyte death in liver injury. Moreover, miR-122 levels were almost normal in patients with cirrhosis without ongoing liver damage, but were elevated when liver injury was present. In contrast to previous assumptions, miR-122-concentrations were independent of the presence of infection/sepsis in mice or human patients. miR-122 levels did not correlate with disease severity or mortality in critically ill patients. In contrast, serum miR-122 levels strictly correlated with the presence of hepatic injury in these patients.
  
  
  CONCLUSIONS
  In mice and humans, miR-122 levels represent an independent and potent marker of ongoing liver injury and hepatic cell death regardless of the underlying disease.
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.forename: Fabian
authors.initials: F
authors.lastname: Benz
authors.forename: David
authors.initials: D
authors.lastname: Vargas Cardenas
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Joern
authors.initials: J
authors.lastname: Janssen
authors.forename: Mihael
authors.initials: M
authors.lastname: Vucur
authors.forename: Jeremie
authors.initials: J
authors.lastname: Gautheron
authors.forename: Anne T
authors.initials: AT
authors.lastname: Schneider
authors.forename: Christiane
authors.initials: C
authors.lastname: Koppe
authors.forename: Karina
authors.initials: K
authors.lastname: Kreggenwinkel
authors.forename: Henning W
authors.initials: HW
authors.lastname: Zimmermann
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
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: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D016923:Cell Death; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D016638:Critical Illness; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D015427:Reperfusion Injury / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse
keywords: critical illness; hepatic failure; liver fibrosis; miR-122; miRNA; serum