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Detection of microRNA Expression in Peritoneal Membrane of Rats Using Quantitative Real-time PCR
Published on: June 27, 2017
Identification of urinary microRNA profiles in rats that may diagnose hepatotoxicity
Xi Yang1, James Greenhaw, Qiang Shi
1Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Abstract:
Circulating microRNAs (miRNAs) have emerged as novel noninvasive biomarkers for several diseases and other types of tissue injury. This study tested the hypothesis that changes in the levels of urinary miRNAs correlate with liver injury induced by hepatotoxicants. Sprague-Dawley rats were administered acetaminophen (APAP) or carbon tetrachloride (CCl(4)) and one nonhepatotoxicant (penicillin/PCN). Urine samples were collected over a 24 h period after a single oral dose of APAP (1250 mg/kg), CCl(4) (2000 mg/kg), or PCN (2400 mg/kg). APAP and CCl(4) induced liver injury based upon increased serum alanine and aspartate aminotransferase levels and histopathological findings, including liver necrosis. APAP and CCl(4) both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl(4). In contrast, PCN caused a slight decrease of a different nonoverlapping set of urinary miRNAs. Cluster analysis revealed a distinct urinary miRNA pattern from the hepatotoxicant-treated groups when compared with vehicle controls and PCN. Analysis of hepatic miRNA levels suggested that the liver was the source of the increased urinary miRNAs after APAP exposure; however, the results from CCl(4) were equivocal. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. Liver gene expression profiling using whole genome microarrays identified eight putative miRNA target genes that were significantly altered in the liver of APAP- and CCl(4)-treated animals. In conclusion, the patterns of urinary miRNA may hold promise as biomarkers of hepatotoxicant-induced liver injury.
Insights
Urinary microRNAs (miRNAs) show distinct patterns following liver injury from hepatotoxicants like acetaminophen and carbon tetrachloride. These urinary miRNA profiles may serve as novel, noninvasive biomarkers for detecting drug-induced liver damage.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Background:
- Circulating microRNAs (miRNAs) are emerging as sensitive, noninvasive biomarkers for various diseases and tissue injuries.
- Urinary miRNAs offer a promising avenue for monitoring organ health due to their accessibility and stability.
Purpose of the Study:
- To investigate the correlation between urinary miRNA levels and liver injury induced by specific hepatotoxicants.
- To identify potential urinary miRNA biomarkers for detecting drug-induced liver injury.
Main Methods:
- Rats were administered acetaminophen (APAP), carbon tetrachloride (CCl(4)), or penicillin (PCN) and monitored for liver injury.
- Urinary and hepatic miRNA levels were analyzed using quantitative real-time PCR and cluster analysis.
- Gene expression profiling identified miRNA target genes in the liver.
Main Results:
- APAP and CCl(4) significantly increased urinary miRNA levels, with 10 miRNAs common to both treatments.
- Penicillin (PCN) induced a distinct, nonoverlapping decrease in urinary miRNAs.
- Distinct urinary miRNA patterns differentiated hepatotoxicant-treated groups from controls.
Conclusions:
- Urinary miRNA profiles exhibit distinct patterns in response to hepatotoxicant-induced liver injury.
- These findings suggest that urinary miRNAs hold promise as noninvasive biomarkers for assessing liver damage caused by toxins.
