Elevated miR‐122 serum levels are an independent marker of liver injury in inflammatory diseases. (21st July 2014)

• Record Type: Journal Article
• Authors: Roderburg, Christoph; Benz, Fabian; Vargas Cardenas, David; Koch, Alexander; Janssen, Joern; Vucur, Mihael; Gautheron, Jeremie; Schneider, Anne T.; Koppe, Christiane; Kreggenwinkel, Karina; Zimmermann, Henning W.; Luedde, Mark; Trautwein, Christian; Tacke, Frank; Luedde, Tom
• Is Part Of: Liver international. Volume 35:Number 4(2015:Apr.)
• Page Start: 1172
• Page End: 1184
• Publication Date: 2014-07-21
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12627
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12627-abs-0001"> <title>Abstract</title> <sec id="liv12627-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>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.</p> </sec> <sec id="liv12627-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="liv12627-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>in vitro</italic> 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.</p> </sec> <sec id="liv12627-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>