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Long nonâcoding RNAs play regulatory roles in acetaminophenâinduced liver injury
- Source :
- Journal of Digestive Diseases. 20:308-317
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Objective To explore the expression profile and role of hepatic long non-coding RNA (lncRNA) in acetaminophen-induced liver injury mouse model by analyzing lncRNA-mRNA co-expression. Methods Serum aminotransferase, liver pathology and inflammatory cells were analyzed in mice model at different time points after treated with acetaminophen 300 mg/kg. High-throughput RNA sequencing was performed to investigate hepatic expression profiles of messenger RNA (mRNA) and lncRNA. The relationship between the lncRNA and mRNA was delineated by the co-expression network using Cytoscape software. Differential mRNAs co-expressed with lncRNAs were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment. Differential mRNAs and lncRNAs were selected for quantitative reverse transcription polymerase chain reaction validation, and the conservation of lncRNA between human and mouse was analyzed. Results Liver injury was more severe at 24 hours than at 6 hours. There was a substantial infiltration of monocytes instead of neutrophil and Kupffer cells at 24 hours compared with 6 hours. The mRNAs co-expressed with the differential lncRNAs at 24 vs 6 hours were mainly enriched in protein processing in endoplasmic reticulum, MAPK and PPAR signaling pathways. The co-expression network delineated with four lncRNAs and 94 mRNAs presented the core position of lncRNA in the network. A conservation analysis indicated that four differential mouse lncRNAs (NONMMUT023651.2, NONMMUT029382.2, NONMMUT029383.2 and NONMMUT102053.1) could all be mapped to the relevant human lncRNAs. Conclusion Four lncRNAs may play regulatory roles through metabolic and apoptosis-related pathways during hepatic homeostasis maintenance and repair progress.
- Subjects :
- Male
Peroxisome proliferator-activated receptor
Apoptosis
Mice
03 medical and health sciences
0302 clinical medicine
Animals
Medicine
KEGG
Acetaminophen
Liver injury
chemistry.chemical_classification
Messenger RNA
business.industry
Gene Expression Profiling
Gastroenterology
RNA
Analgesics, Non-Narcotic
medicine.disease
Long non-coding RNA
Cell biology
Mice, Inbred C57BL
Reverse transcription polymerase chain reaction
Gene Ontology
Liver
chemistry
Chemical and Drug Induced Liver Injury, Chronic
030220 oncology & carcinogenesis
RNA, Long Noncoding
030211 gastroenterology & hepatology
Signal transduction
business
Signal Transduction
Subjects
Details
- ISSN :
- 17512980 and 17512972
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of Digestive Diseases
- Accession number :
- edsair.doi.dedup.....27dc1f666110ed353f0040fa73e5fa84