MicroRNAs in Liver Disease: Bench to Bedside

Shah, Niraj James; Nelson, James E.; Kowdley, Kris V.

doi:10.1016/j.jceh.2013.09.001

Cited by 25 publications

(16 citation statements)

References 159 publications

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“…On the other hand, although lots of technical challenges remain, many miRNAs represent promising targets for therapeutic gene therapy approaches . The studies discussed in the review suggest that targeting multiple miRNAs that regulate one target gene or multiple target genes controlling one particular process may provide an optimal therapeutic strategy.…”

Section: Resultsmentioning

confidence: 99%

‘Micro‐managers’ of hepatic lipid metabolism and NAFLD

et al. 2015

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Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD, hepatic steatosis develops as a consequence of metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG) export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play critical roles in various biological processes through regulating gene expression at post-transcriptional level. A growing body of evidence suggests that miRNAs not only maintain hepatic TG homeostasis under physiological condition, but also participate in the pathogenesis of NAFLD. In this review, we focus on the current knowledge of the hepatic miRNAs associated with the development of liver steatosis and the regulatory mechanisms involved, which might be helpful to further understand the nature of NAFLD and provide a sound scientific basis for the drug development.

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Section: Resultsmentioning

confidence: 99%

‘Micro‐managers’ of hepatic lipid metabolism and NAFLD

et al. 2015

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“…Numerous studies have identified microRNAs, which are small, single‐stranded noncoding regulatory RNA molecules, as possible sensitive biomarkers for DILI . Notably, microRNA‐122 (miR‐122) is elevated earlier and demonstrates increased sensitivity in patients with acetaminophen‐induced liver injury compared with ALT .…”

mentioning

confidence: 99%

Exploration of Biomarkers for Amoxicillin/Clavulanate‐Induced Liver Injury: Multi‐Omics Approaches

Lee

Kim

et al. 2016

Clinical Translational Sci

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To explore potential biomarkers for amoxicillin/clavulanate‐induced liver injury (AC‐DILI), we conducted a clinical trial in 32 healthy subjects based on multi‐omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver‐specific microRNA‐122 (miR‐122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC‐DILI. We also identified urinary metabolites, such as azelaic acid and 7‐methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration (P < 0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC‐DILI, including metabolic changes, increased miR‐122 level, increased liver enzyme activity, and enhanced lymphocyte proliferation after drug administration. In conclusion, this study provides potential biomarkers for AC‐DILI based on currently known mechanisms using comprehensive multi‐omics approaches.

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“…Circulating miRs are found in lipid or lipoprotein complexes providing an association between plasma miR levels and specifi c organ dysfunction [15]. miRs modulate diverse cellular processes associated with liver injury as infl ammation, apoptosis, and hepatocyte regeneration [16]. The miR-122 is liver specifi c and accounts for approximately 70% of all miRs in the liver [15].…”

Section: Micrornasmentioning

confidence: 99%