MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice
| Autor: | Sho Akai, Yasuaki Uematsu, Tsuyoshi Yokoi, Shingo Oda, Toru Yamada, Tomoaki Tochitani |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Lymphoid Enhancer-Binding Factor 1 Toxicology SOXC Transcription Factors 03 medical and health sciences SOX4 Th2 Cells Immune system Internal medicine microRNA medicine Animals Enhancer Transcription factor Pharmacology Liver injury Mice Inbred BALB C Methimazole biology Alanine Transaminase medicine.disease Glutathione MicroRNAs 030104 developmental biology Endocrinology Liver Alanine transaminase biology.protein Female Chemical and Drug Induced Liver Injury Lymphoid enhancer-binding factor 1 |
| Zdroj: | Toxicology and Applied Pharmacology. 307:1-9 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2016.07.008 |
| Popis: | MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. |
| Databáze: | OpenAIRE |
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