Transcriptomic analysis reveals the mechanism of sulfasalazine-induced liver injury in mice
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ABSTRACT:
PROVIDER: PRJNA587500 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10398930_1.fastq.gz | Fastqsanger.gz | |||
| SRR10398930_2.fastq.gz | Fastqsanger.gz | |||
| SRR10398931_1.fastq.gz | Fastqsanger.gz | |||
| SRR10398931_2.fastq.gz | Fastqsanger.gz | |||
| SRR10398932_1.fastq.gz | Fastqsanger.gz |
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Project description:Liver injury is one of the main toxic effect of sulfasalazine (SASP). However, the toxicological mechanism of SASP-induced liver injury remains unclear. In the present study, the liver injury was induced by orally treatment with SASP for 4 weeks in mice. The hepatic mRNA profiles were detected by RNA sequencing and the differentially expressed genes (DEGs) were analyzed by bioinformatics methods. The elevated serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL), combined with the hepatic histopathological features verified that liver injury was successfully caused by SASP. Transcriptomic results showed that 187 genes (fold change > 1.5 and P < 0.05) were differentially expressed, of which 106 genes were up-regulated and 81 genes were down-regulated in SASP-treated group. Moreover, the further analysis showed that these 187 differentially expressed genes (DEGs) were enriched in 123 GO terms, which mainly including oxidation-reduction process, oxidoreductase activity and epoxygenase P450 pathway. KEGG pathway analysis showed 30 pathways including chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism and glutathione metabolism. Among these 187 DEGs, the top 22 hub genes were screened from network of protein-protein interaction (PPI) and verified by qRT-PCR. The results showed that the mRNA levels of hepatic drug-metabolizing enzymes, including cyp2b50, cyp2c50, cyp2c39, cyp2c38, cyp2c29, cyp2c54, cyp2c55, cyp2a5, gsta1, gsta2, gstt2, gstm2 and ephx1, were significantly up-regulated in SASP-treated group. Moreover, the expression of egfr, which has the highest score in PPI degree, were significantly down-regulated in SASP-treated group. The present study suggested that the toxicological mechanisms of SASP-induced liver injury might be related to multi-biological processes and pathways. Our results would be helpful for better understanding the hepatotoxic mechanism of SASP. However, the precise mechanism still needs further research.
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