The altered liver microRNA profile in hepatotoxicity induced by rhizome Dioscorea bulbifera in mice.
MicroRNA (miRNA) has been reported to play important roles in regulating drug-induced liver injury. Ethyl acetate extract isolated from rhizoma Dioscoreae bulbifera (EF) has been reported to induce hepatotoxicity in our previous studies. This study aims to observe the altered liver miRNA profile and its related signalling pathway involved in EF-induced hepatotoxicity. Serum alanine/aspartate aminotransferase assay showed that EF (450 mg/kg)-induced hepatotoxicity in mice. Results of miRNA chip analysis showed that the expression of eight miRNAs was up-regulated and of other nine miRNAs was down-regulated in livers from EF-treated mice. Further, the altered expression of miR-200a-3p, miR-5132-5p and miR-5130 was validated using real-time polymerase chain reaction (PCR) assay. There were total seven predicted target genes of miR-200a-3p, miR-5132-5p and miR-5130. Only one kyoto encyclopedia genes and genomes pathway was annotated using those target genes, which is protein processing in endoplasmic reticulum (ER). Furthermore, liver expression of DnaJ subfamily A member 1, a key gene involved in protein processing in ER based on the altered miRNAs, was increased in EF-treated mice. In conclusion, the results demonstrated that EF altered the expression of liver miRNA profile and its related signalling pathway, which may be involved in EF-induced hepatotoxicity.
1 Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Rui
R
Yang
2 Shanghai Key Laboratory of Complex Prescription, MOE Key Laboratory for Standardization of Chinese Medicines, SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Qingyun
Q
Bai
2 Shanghai Key Laboratory of Complex Prescription, MOE Key Laboratory for Standardization of Chinese Medicines, SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jiaqi
J
Zhang
1 Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yuchen
Y
Sheng
2 Shanghai Key Laboratory of Complex Prescription, MOE Key Laboratory for Standardization of Chinese Medicines, SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Lili
L
Ji
D000818:Animals; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D027742:Dioscorea / Q000737:chemistry*; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D011897:Random Allocation; D027343:Rhizome / Q000737:chemistry*; D013047:Specific Pathogen-Free Organisms; D059467:Transcriptome / Q000187:drug effects*
D015415:Biomarkers; D035683:MicroRNAs; D010936:Plant Extracts
Dnaja1; Rhizoma Dioscoreae bulbifera; hepatotoxicity; miRNA