Long non‐coding RNAs play regulatory roles in acetaminophen‐induced liver injury
Autor: | Tai-hua Yang, Feng Xue, Jian Xin Zheng, Qiang Xia, Jin Chuan Liu, Xiang Qian Gu, Tian Qin, Yuanjia Tang |
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Rok vydání: | 2019 |
Předmět: |
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 |
Zdroj: | Journal of Digestive Diseases. 20:308-317 |
ISSN: | 1751-2980 1751-2972 |
DOI: | 10.1111/1751-2980.12749 |
Popis: | 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. |
Databáze: | OpenAIRE |
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