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A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
[The Correlation Between MicroRNAs in Serum and the Extent of Liver Injury]
Yi-Nan Zuo1,2, Xue-Ling He2, Xue-Ni Shi1,2
1College of Life Sciences, Sichuan University, Chengdu 610065, China.
Objectives:
To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl4 induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS).
Methods:
The acute liver injury model in rat by CCl4 (1.5 mL/kg), and the acute liver injury model in mice by APAP (160 mg/kg) were established. The serum at different time points on both models were collected respectively. The absolute quantification of microRNAs in serum were detected by using MiRbayTM SV miRNA Assay kit. Meanwhile, the pathological sections of liver tissue of the mice at each time point were collected to analyze the correlation between microRNAs and the degree of liver injury.
Results:
In CCl4-induced rat acute liver injury model and APAP induced mouse acute liver injury, miR-122 and miR-192 appeared to be rising significantly, which remained the highest level at 24 h after treatment, and declined to the normal level after 72 h. In CCl4-induced rat acute liver injury model, the change of miR-92a was fluctuated and had no apparent rules, miR-451 declined gradually, but not obviously. In mice acute liver injury model induced by APAP, miR-92a and miR-451 in the progress of liver injury declined gradually, reached the lowest point at 48 h, and then recovered. The result of correlation analysis indicated that miR-122 and miR-192 presented a good positive correlation with the DILI-PSS ( r=0.741 3, P<0.05; r=0.788 3, P<0.01).
Conclusions:
The absolute quantification of miR-122 and miR-192 in serum has the highest level in 24 h, then decrease in 72 h, in both drug-induced and chemical liver injury. In addition, both the two microRNAs have good correlation with DILI-PSS in APAP-induced liver injury models.
Insights
Serum miR-122 and miR-192 levels accurately indicate acute liver injury severity in animal models. These microRNAs (miRNAs) show a strong correlation with liver damage, aiding in diagnosis and monitoring of drug-induced liver injury (DILI).
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Acute liver injury (ALI) poses a significant health concern, necessitating reliable biomarkers for diagnosis and monitoring.
- MicroRNAs (miRNAs) are small non-coding RNAs with critical roles in gene regulation and are increasingly recognized as potential biomarkers for various diseases, including liver injury.
Purpose of the Study:
- To investigate the correlation between serum levels of specific microRNAs (miR-122, miR-451, miR-92a, miR-192) and the extent of acute liver injury in rat and mouse models.
- To assess the relationship between these serum microRNAs and the drug-induced liver injury pathological scoring system (DILI-PSS).
Main Methods:
- Established rat models of carbon tetrachloride (CCl4)-induced ALI and mouse models of acetaminophen (APAP)-induced ALI.
- Collected serum samples at various time points post-induction and quantified miRNA absolute levels using the MiRbay SV miRNA Assay kit.
- Analyzed liver tissue pathology to correlate miRNA levels with injury severity.
Main Results:
- Serum miR-122 and miR-192 levels significantly increased in both CCl4-induced rat and APAP-induced mouse ALI models, peaking at 24 hours and returning to baseline by 72 hours.
- miR-122 and miR-192 demonstrated a strong positive correlation with the DILI-PSS (r=0.7413, P<0.05; r=0.7883, P<0.01, respectively).
- Changes in miR-92a and miR-451 levels were less consistent or showed gradual decline in specific models.
Conclusions:
- Absolute quantification of serum miR-122 and miR-192 serves as a reliable indicator of acute liver injury, with levels peaking at 24 hours and decreasing by 72 hours.
- These two microRNAs exhibit a significant positive correlation with DILI-PSS, particularly in APAP-induced liver injury models.
- miR-122 and miR-192 are promising biomarkers for assessing the severity of drug-induced and chemical liver injuries.
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