Long non-coding RNAs play regulatory roles in acetaminophen-induced liver injury. 2019

Jian Xin Zheng, and Yuan Jia Tang, and Tai Hua Yang, and Tian Qin, and Jin Chuan Liu, and Xiang Qian Gu, and Feng Xue, and Qiang Xia
Department of Liver Surgery and Liver Transplantation Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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. CONCLUSIONS Four lncRNAs may play regulatory roles through metabolic and apoptosis-related pathways during hepatic homeostasis maintenance and repair progress.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000082 Acetaminophen Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056487 Chemical and Drug Induced Liver Injury, Chronic Liver disease lasting six months or more, caused by an adverse effect of a drug or chemical. The adverse effect may be caused by drugs, drug metabolites, chemicals from the environment, or an idiosyncratic response. Chronic Drug-Induced Liver Injury,Drug-Induced Liver Injury, Chronic,Liver Injury, Drug-Induced, Chronic,Chemical-Induced Liver Injury, Chronic,Chemically-Induced Liver Injury, Chronic,Hepatitis, Chronic, Drug-Induced,Hepatitis, Chronic, Drug-Related,Chemical Induced Liver Injury, Chronic,Chemically Induced Liver Injury, Chronic,Chronic Drug Induced Liver Injury,Drug Induced Liver Injury, Chronic
D062085 RNA, Long Noncoding A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin. LincRNA,RNA, Long Untranslated,LINC RNA,LincRNAs,Long Intergenic Non-Protein Coding RNA,Long Non-Coding RNA,Long Non-Protein-Coding RNA,Long Noncoding RNA,Long ncRNA,Long ncRNAs,RNA, Long Non-Translated,lncRNA,Long Intergenic Non Protein Coding RNA,Long Non Coding RNA,Long Non Protein Coding RNA,Long Non-Translated RNA,Long Untranslated RNA,Non-Coding RNA, Long,Non-Protein-Coding RNA, Long,Non-Translated RNA, Long,Noncoding RNA, Long,RNA, Long Non Translated,RNA, Long Non-Coding,RNA, Long Non-Protein-Coding,Untranslated RNA, Long,ncRNA, Long,ncRNAs, Long

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