miR-223 represents a biomarker in acute and chronic liver injury

Schueller, Florian; Roy, Sanchari; Loosen, Sven H.; Alder, Jan; Koppe, Christiane; Schneider, Anne T.; Wandrer, Franziska; Bantel, Heike; Vucur, Mihael; Mi, Qing‐Sheng; Luedde, Tom; Roderburg, Christoph

doi:10.1042/cs20170218

Cited by 34 publications

(32 citation statements)

References 35 publications

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“…However, a recent study suggests that miR‐223 does not play a role in controlling acute liver injury in several mouse models and in controlling liver fibrosis induced by chronic CCl 4 treatment . Part of the reason for the discrepancy between that study’s results and ours may be the different wild‐type (WT) control mice used (WT littermate control mice were used in our study but not in the other study). Interestingly, several recent studies have reported that levels of miR‐223 were up‐regulated in the liver in a mouse model of NASH and elevated in the serum in NASH patients .…”

contrasting

confidence: 57%

“…We have previously demonstrated that miR‐223 plays an important role in attenuating alcoholic liver injury and acetaminophen‐induced liver injury by targeting interleukin‐6 ( Il6 ) and inhibitor of nuclear factor kappa B (NF‐κB) kinase subunit alpha genes in neutrophils . However, a recent study suggests that miR‐223 does not play a role in controlling acute liver injury in several mouse models and in controlling liver fibrosis induced by chronic CCl 4 treatment . Part of the reason for the discrepancy between that study’s results and ours may be the different wild‐type (WT) control mice used (WT littermate control mice were used in our study but not in the other study).…”

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confidence: 56%

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MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes

et al. 2019

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Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to more severe forms of liver injury including nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). In humans, only 20%-40% of patients with fatty liver progress to NASH, and mice fed a high-fat diet (HFD) develop fatty liver but are resistant to NASH development. To understand how simple steatosis progresses to NASH, we examined hepatic expression of anti-inflammatory microRNA-223 (miR-223) and found that this miRNA was highly elevated in hepatocytes in HFD-fed mice and in human NASH samples. Genetic deletion of miR-223 induced a full spectrum of NAFLD in long-term HFD-fed mice including steatosis, inflammation, fibrosis, and HCC. Furthermore, microarray analyses revealed that, compared to wild-type mice, HFD-fed miR-223 knockout (miR-223KO) mice had greater hepatic expression of many inflammatory genes and cancer-related genes, including (C-X-C motif) chemokine 10 (Cxcl10) and transcriptional coactivator with PDZ-binding motif (Taz), two well-known factors that promote NASH development. In vitro experiments demonstrated that Cxcl10 and Taz are two downstream targets of miR-223 and that overexpression of miR-223 reduced their expression in cultured hepatocytes. Hepatic levels of miR-223, CXCL10, and TAZ mRNA were elevated in human NASH samples, which positively correlated with hepatic levels of several miR-223 targeted genes as well as several proinflammatory, cancer-related, and fibrogenic genes. Conclusion: HFD-fed miR-223KO mice develop a full spectrum of NAFLD, representing a clinically relevant mouse NAFLD model; miR-223 plays a key role in controlling steatosis-to-NASH progression by inhibiting hepatic Cxcl10 and Taz expression and may be a therapeutic target for the treatment of NASH. (Hepatology 2019;70:1150-1167).

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confidence: 57%

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confidence: 56%

MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes

et al. 2019

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“…Asterisks indicate whether there were significant differences among the groups. *P < 0.05; **P < 0.01. www.nature.com/scientificreports www.nature.com/scientificreports/ was detected; (iii) and previously published data regarding the miRNAs profile in decompensated cirrhosis 17,18 , inflammation 19,20 , and sepsis [21][22][23] .…”

Section: Discussionmentioning

confidence: 78%

“…Based on the magnitude of expression difference between patients with and without ACLF in the microarray analysis and in literature reports [17][18][19][20][21][22][23] miRNAs miR-106b-5p, miR-126-3p, miR-20a-5p, miR-223-3p, and miR-25-3p were selected to be further validated by RT-qPCR. Some miRNAs that had high FC values such as let-7a-5p and let-7g-5p were not detected in most microarray samples and were therefore not included in the validation step.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

Cisilotto

Amaral

Rosolen

et al. 2020

Sci Rep

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Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twentyseven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality. The natural history of cirrhosis is usually characterized by a long-standing compensated phase followed by a transition to the decompensated disease, identified by the occurrence of specific complications of cirrhosis, such as ascites, variceal bleeding, and hepatic encephalopathy 1. Patients with both compensated or decompensated cirrhosis are at risk of progression to acute-on-chronic liver failure (ACLF), a condition characterized by an acute deterioration of the liver function and characterized by progression to extrahepatic organ failure and high short-term mortality 2,3. Although a precise definition is still lacking, the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium definition is one of the most validated criteria for ACLF in patients with cirrhosis and it is based on a modified version of SOFA score called CLIF-SOFA 2,4. According to a recently published study 5 , mortality rates in ACLF patients are 25.5% and 40% in 28 and 90 days of admission, respectively. Therefore, searching for new biomarkers associated with the presence of ACLF and prognosis of patients with acute decompensation of cirrhosis may improve clinical decision and help to implement risk-adapted treatment strategies. In recent years, miRNAs have been studied as promising biomarkers for the diagnosis and prognostic in many clinical scenarios 6-8 , including liver diseases 9. The miRNAs are a group of small non-coding RNAs, with approximately 22 nucleotides, which post-transcriptionally regulate gene expression

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“…In acute and chronic liver injury models, hepatic miR-223 up-regulation was restricted to hepatocytes, and correlated with the degree of liver injury and hepatic cell death. Moreover, elevated miR-223 expression was significantly higher in the serum, following acute liver injury [36].…”

Section: Micrornasmentioning

confidence: 92%

Biomarkers of Liver Injury during Transplantation in an Era of Machine Perfusion

Bhogal

Mirza

Afford

et al. 2020

IJMS

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Liver ischaemia–reperfusion injury (IRI) is an intrinsic part of the transplantation process and damages the parenchymal cells of the liver including hepatocytes, endothelial cells and cholangiocytes. Many biomarkers of IRI have been described over the past two decades that have attempted to quantify the extent of IRI involving different hepatic cellular compartments, with the aim to allow clinicians to predict the suitability of donor livers for transplantation. The advent of machine perfusion has added an additional layer of complexity to this field and has forced researchers to re-evaluate the utility of IRI biomarkers in different machine preservation techniques. In this review, we summarise the current understanding of liver IRI biomarkers and discuss them in the context of machine perfusion.

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miR-223 represents a biomarker in acute and chronic liver injury

Abstract: miR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis.

Cited by 34 publications

References 35 publications

MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes

MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

Biomarkers of Liver Injury during Transplantation in an Era of Machine Perfusion

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