Transcriptomic profiling of mouse enteroids exposure to indomethacin

Abstract

Objective To characterize the changes in transcriptome of mouse enteroids exposed to indomethacin. Methods The viability of enteroids exposed to indomethacin was measured using MTT staining. The differentially expressed genes (DEGs) between the control group and the indomethacin group were identified using Illumina Hiseq sequencing systems. The functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were mapped in Gene Ontology (GO) and KEGG pathway database, respectively. Results The MTT results showed that the survival rates of mouse enteroids exposed to indomethacin at concentrations of 100, 250, 300, 400 and 500 μM for 48 h were 80.34%, 70.17%, 61.94%, 54.38% and 42.22%. The survival rates of enteroids were 80.56%, 70.17% and 59.30% at 250 μM of indomethacin treatment for 24 h, 48 h and 72 h respectively. For cellular component, several GO terms were identified, especially those associated with microbody and peroxisome (P<0.01). The GO terms for biological process with DEGs were mostly in the category of organic acid metabolic process, oxoacid metabolic process and carboxylic acid metabolic process (P<0.01). Most of the molecular functional GO terms associated with DEGs fell into the category of oxidoreductase activity, glutathione transferase activity and carboxylic acid binding (P<0.01). The KEGG pathway enrichment analyses revealed that the DEGs were primarily associated with chemical carcinogenesis, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, PPAR signaling pathway (P<0.01). Conclusions Indomethacin inhibits the growth of mouse enteroids. There may be some mechanisms of defence against oxidative stress to protect enteroids from NSAIDs-induced injury. Targeting oxidative stress with anti-oxidant therapy would be an effective therapeutic strategy. Key words: Indomethacin; Enteroids; High-throughput sequencing