Elevated miR-122 Serum Levels Are an Independent Marker of Liver Injury in Inflammatory Diseases

Liver Int. 2015 Apr;35(4):1172-84. doi: 10.1111/liv.12627. Epub 2014 Jul 21.

Abstract

Background & aims: 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.

Conclusion: 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.

Keywords: critical illness; hepatic failure; liver fibrosis; miR-122; miRNA; serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Case-Control Studies
  • Cell Death
  • Chemical and Drug Induced Liver Injury / blood*
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / pathology
  • Critical Illness
  • Disease Models, Animal
  • Female
  • Genetic Markers
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / blood*
  • Middle Aged
  • Reperfusion Injury / blood*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / pathology
  • Sepsis / blood*
  • Sepsis / diagnosis
  • Sepsis / genetics
  • Sepsis / pathology
  • Up-Regulation
  • Young Adult

Substances

  • Genetic Markers
  • MIRN122 microRNA, human
  • MicroRNAs
  • Mirn122 microRNA, mouse