Elevated miR‐122 serum levels are an independent marker of liver injury in inflammatory diseases

Roderburg, Christoph; Benz, Fabian; Cardenas, David Vargas; Koch, Alexander; Janssen, Joern; Vucur, Mihael; Gautheron, Jérémie; Schneider, Anne T.; Koppe, Christiane; Kreggenwinkel, Karina; Zimmermann, Henning W.; Luedde, Mark; Trautwein, Christian; Tacke, Frank; Luedde, Tom

doi:10.1111/liv.12627

Cited by 101 publications

(94 citation statements)

References 46 publications

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“…Moreover, we compared expression levels of miR-192-5p between different hepatic cell compartments. miR-192-5p expression was restricted to hepatocytes (Supplementary Figure S1B), suggesting that -similar to miR-122 [21] -it represents a miRNA relatively specific for the liver and hepatocytes.…”

Section: Mir-192-5p Is Primarily Expressed In the Liver And Is Down-rmentioning

confidence: 90%

“…Finally, we analysed miR-192-5p serum levels in 223 critically ill patients and 76 respective controls. This cohort has been previously described [21], and characteristics of the population are given in Supplementary Table S1.…”

Section: Patient Cohorts Analysedmentioning

confidence: 99%

“…Statistical analyses were performed as described previously [21]. Data from humans are given as median and range considering the skewed distribution of most parameters.…”

Section: Statisticsmentioning

confidence: 99%

“…Blood samples were taken by a small team of trained physicians according to the protocol and miRNA extraction from serum was performed as described recently [21,23].…”

Section: Mirna Isolation From Serummentioning

confidence: 99%

“…Immune cells and hepatocytes were isolated from livers of mice after I/R procedure as described recently [21].…”

Section: Isolation Of Hepatic Immune Cells and Hepatocytesmentioning

confidence: 99%

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Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury

et al. 2016

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miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury.

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Section: Mir-192-5p Is Primarily Expressed In the Liver And Is Down-rmentioning

confidence: 90%

Section: Patient Cohorts Analysedmentioning

confidence: 99%

“…Statistical analyses were performed as described previously [21]. Data from humans are given as median and range considering the skewed distribution of most parameters.…”

Section: Statisticsmentioning

confidence: 99%

“…Blood samples were taken by a small team of trained physicians according to the protocol and miRNA extraction from serum was performed as described recently [21,23].…”

Section: Mirna Isolation From Serummentioning

confidence: 99%

“…Immune cells and hepatocytes were isolated from livers of mice after I/R procedure as described recently [21].…”

Section: Isolation Of Hepatic Immune Cells and Hepatocytesmentioning

confidence: 99%

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Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury

et al. 2016

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Dynamic changes of serum microRNA‐122‐5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation

Koyama

Kuragaichi²,

Sato

et al. 2016

ESC Heart Failure

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Aims Recent studies have shown that serum microRNA (miR) abundance is informative for the diagnosis or prognosis of heart failure. However, the dynamics and kinetics of miRs in acute heart failure are largely unknown. Serial measurement and analysis of serum miRs changes in individuals along their therapeutic course could reduce inter-individual variation and should detect potentially important serum miRs related to disease mechanisms. Based on this concept, we profiled serum miR signatures of blood samples that were obtained sequentially on the day of admission and on hospital Day 7.Methods and results This prospective, observational study included 42 consecutive acute heart failure patients (74 AE 1 years old, 24 male). From admission to Day 7, most of the patients showed clinical improvement. In such a cohort, we detected several fluctuations of serum miRs by two distinct screening methods (quantitative PCR and high-throughput sequencing). One of these fluctuating serum miRs, miR-122-5p, decreased significantly from Day 1 to Day 7 [median arbitrary unit (1st:3rd quantile value); 4.62 [2.39:12.3] to 3.07 [1.67:5.39], P = 0.007]. This fluctuation was significantly correlated with changes in serum liver function markers (estimated coefficient and 95% confidence interval; vs change in aspartate aminotransferase 1.69, 0.890-2.484, P < 0.001 and r = 0.560, vs change in alanine aminotransferase 1.09, 0.406-1.771, P = 0.007 and r = 0.428).Conclusions The serum miR signature of patients with acute heart failure might indicate the severity of the disease or patients' response to therapeutic intervention. Notably, serum miR-122-5p levels reflect liver damage in this condition.

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Retracted: Tanshinol relieves lipopolysaccharide‐induced inflammatory injury of HaCaT cells via down‐regulation of microRNA‐122

Wang

Wei²

2019

Phytotherapy Research

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This study investigated the effects of tanshinol (TAN) on lipopolysaccharide (LPS)induced human keratinocytes inflammatory injury and underlying potential molecular mechanisms. Viability and apoptosis of HaCaT cells were assessed using MTT assay and Annexin V-FITC/PI staining, respectively. Quantitative reverse transcription-polymerase chain reaction was performed to measure the expression of microRNA-122 (miR-122) in HaCaT cells. Cell transfection was conducted to up-regulate the expression of miR-122. Western blotting was used to detect the protein expression levels of key factors involved in cell apoptosis, inflammatory response, c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF-κB) pathways. We found that LPS treatment induced HaCaT cell inflammatory injury by inhibiting cell viability, promoting cell apoptosis, and enhancing the protein expression levels of cyclooxygenase 2 and inducible nitric oxide synthase. TAN treatment relieved LPS-induced HaCaT cell inflammatory injury. Moreover, TAN treatment attenuated LPS-induced activation of JNK and NF-κB pathways in HaCaT cells. Furthermore, TAN treatment alleviated LPS-induced up-regulation of miR-122. Overexpression of miR-122 reversed the effects of TAN on LPS-induced HaCaT cell inflammatory injury and activation of JNK and NF-κB pathways. In conclusion, TAN exerted anti-inflammatory and protective effects on keratinocytes injury. TAN relieved LPS-induced inflammatory injury of human HaCaT cells via downregulating miR-122 and then inactivating JNK and NF-κB pathways.

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Elevated miR‐122 serum levels are an independent marker of liver injury in inflammatory diseases

Abstract: 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.

Cited by 101 publications

References 46 publications

Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury

Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury

Dynamic changes of serum microRNA‐122‐5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation

Retracted: Tanshinol relieves lipopolysaccharide‐induced inflammatory injury of HaCaT cells via down‐regulation of microRNA‐122

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