Expression of miRNA-122 Induced by Liver Toxicants in Zebrafish

Nam, Hyun-Sik; Hwang, Kyu-Seok; Jeong, Yun-Mi; Ryu, Jeong-Im; Choi, Tae–Young; Bae, Myung‐Ae; Son, Woo‐Chan; You, Kwan‐Hee; Son, Hyeon-Taek; Kim, Cheol‐Hee

doi:10.1155/2016/1473578

Cited by 19 publications

(10 citation statements)

References 30 publications

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“…In past studies on rats [51,52], the miR-122 levels in healthy liver tissue increased, while toxic substances and diseases increase miR-122 expression in the serum. In zebrafish [53], the toxic liver damage induced by tamoxifen or APAP increased the expression of hepatic specific miR-122 in liver tissue. In dogs with liver disease, the expression of miR-122 in serum was significantly higher than that in healthy dogs [54].…”

Section: Discussionmentioning

confidence: 99%

“…This molecule plays a key role in liver physiology, where it participates in hepatocyte differentiation, supports spontaneous regeneration, and takes part in liver homeostasis, lipid metabolism, and cholesterol synthesis [33]. In addition, many studies have shown the sensitivity and specificity of miR-122 as a circulating biomarker of liver injury in animals, such as chimpanzees [50], mice [30], rats [51,52], zebrafish [53], and dogs [54]. The literature also reported the potential use of miR-122 in humans as a biomarker for liver diseases caused, among others, by drug-induced liver injury (DILI) [29,55], hepatitis B and C [25,56], and ethanol consumption [57].…”

Section: Discussionmentioning

confidence: 99%

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Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection

Hukowska-Szematowicz

Maciejak-Jastrzębska

Blatkiewicz

et al. 2020

Viruses

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Current knowledge on the role of microRNAs (miRNAs) in rabbit hemorrhagic disease virus (RHDV) infection and the pathogenesis of rabbit hemorrhagic disease (RHD) is still limited. RHDV replicates in the liver, causing hepatic necrosis and liver failure. MiRNAs are a class of short RNA molecules, and their expression profiles vary over the course of diseases, both in the tissue environment and in the bloodstream. This paper evaluates the expression of miRNAs in the liver tissue (ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p) and serum (ocu-miR-122-5p) of rabbits experimentally infected with RHDV. The expression levels of ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p in liver tissue were determined using reverse transcription quantitative real-time PCR (RT-qPCR), and the expression level of circulating ocu-miR-122-5p was established using droplet digital PCR (ddPCR). The expression levels of ocu-miR-155-5p and ocu-miR-16b-5p were significantly higher in the infected rabbits compared to the healthy rabbits (a fold-change of 5.8 and 2.5, respectively). The expression of ocu-miR-122-5p was not significantly different in the liver tissue from the infected rabbits compared to the healthy rabbits (p = 0.990), while the absolute expression level of the circulating ocu-miR-122-5p was significantly higher in the infected rabbits than in the healthy rabbits (p < 0.0001). Furthermore, a functional analysis showed that ocu-miR-155-5p, ocu-miR-16b-5p, and ocu-miR-122-5p can regulate the expression of genes involved in processes correlated with acute liver failure (ALF) in rabbits. Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that the potential target genes of the three selected miRNAs may interact with each other in different pathways. The results indicate the roles of these miRNAs in RHDV infection and over the course of RHD and may reflect hepatic inflammation and impairment/dysfunction in RHD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection

Hukowska-Szematowicz

Maciejak-Jastrzębska

Blatkiewicz

et al. 2020

Viruses

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show abstract

“…miR‐122 is highly expressed in hepatocytes accounting for up to 70% of the total liver miRNA content . Multiple studies have demonstrated the sensitivity and specificity of miR‐122 as a circulating biomarker of liver injury in chimpanzees, mice, rats, zebrafish, and in human studies of different liver diseases including drug‐induced liver injury (DILI), hepatitis C, and ethanol consumption . miR‐122 has received regulatory support for further qualification by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the context of DILI .…”

Section: Introductionmentioning

confidence: 99%

Sensitivity and specificity of microRNA‐122 for liver disease in dogs

Oosthuyzen

Berg

Francis

et al. 2018

Veterinary Internal Medicne

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BackgroundCurrent tests for diagnosing liver disease in dogs are sub‐optimal. MicroRNA‐122 (miR‐122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR‐122 could have utility in identifying dogs with liver disease.ObjectiveEstablish the reference interval for miR‐122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non‐liver disease.AnimalsStored serum from 120 healthy dogs, 100 dogs with non‐liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed.MethodsRetrospective study. Medical records of dogs with liver disease, non‐liver disease and healthy dogs were reviewed. Serum miR‐122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements.ResultsIn healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR‐122 were 110 (90% CI 80‐114), 594 (505‐682), and 3312 (2925‐5144) copies/μL, respectively. There was no difference between healthy dogs and dogs with non‐liver disease (median ± IQR: healthy dogs 609 [327‐1014] copies/μL; non‐liver disease 607 [300‐1351] copies/μL). miR‐122 was higher in dogs with liver disease (11 332 [4418‐20 520] copies/μL, P < .001 compared to healthy dogs). miR‐122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86‐0.99]). The upper limit of normal for healthy dogs (3312 copies/μL) had a sensitivity of 77% and specificity of 97% for identifying liver disease.Conclusion and Clinical ImportanceLiver disease can be sensitively and specifically diagnosed in dogs by measurement of miR‐122.

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“…As a result, they concluded that in adult zebrafish, the same hepatotoxicant specifically alters the expression of genes encoding albumin-like protein, ceruloplasmin, liver fatty acid binding protein (L-Fabp10a), and transferrin, all of them regarded as biomarkers of hepatotoxicity 75 . In addition, liver expression of miR-122, a liver-specific toxicity biomarker in mammals, was also reported to be a possible biomarker of hepatotoxicity in zebrafish 76 .…”

Section: Examples Of Applicationsmentioning

confidence: 99%

Application of zebrafish to safety evaluation in drug discovery

Miyawaki

2020

J Toxicol Pathol

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Traditionally, safety evaluation at the early stage of drug discovery research has been done using in silico , in vitro , and in vivo systems in this order because of limitations on the amount of compounds available and the throughput ability of the assay systems. While these in vitro assays are very effective tools for detecting particular tissue-specific toxicity phenotypes, it is difficult to detect toxicity based on complex mechanisms involving multiple organs and tissues. Therefore, the development of novel high throughput in vivo evaluation systems has been expected for a long time. The zebrafish ( Danio rerio ) is a vertebrate with many attractive characteristics for use in drug discovery, such as a small size, transparency, gene and protein similarity with mammals (80% or more), and ease of genetic modification to establish human disease models. Actually, in recent years, the zebrafish has attracted interest as a novel experimental animal. In this article, the author summarized the features of zebrafish that make it a suitable laboratory animal, and introduced and discussed the applications of zebrafish to preclinical toxicity testing, including evaluations of teratogenicity, hepatotoxicity, and nephrotoxicity based on morphological findings, evaluation of cardiotoxicity using functional endpoints, and assessment of seizure and drug abuse liability.

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Expression of miRNA-122 Induced by Liver Toxicants in Zebrafish

Cited by 19 publications

References 30 publications

Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection

Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection

Sensitivity and specificity of microRNA‐122 for liver disease in dogs

Application of zebrafish to safety evaluation in drug discovery

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