ER-464195-01 regulates the expression of inflammation-related genes in DSS-treated mice. Mus musculus

We identified a small molecule, orally active ER-464195-01, inhibits the calreticulin binding to alpha integrins, and clearly suppresses the adherence ability of leukocytes. Our transcriptome analysis with the colon of dextran sodium sulfate (DSS)-treated mice reveals that the increased expression of pro-inflammatory genes was down-regulated by ER-464195-01. Purpose: To gain insight into the molecular mechanisms underlying the prevention of DSS-induced colitis conferred by treatment of ER-464195-01, we performed a comprehensive analysis of ER-464195-01-mediated gene expression changes in DSS-induced colitis using RNA sequencing (RNA-Seq). Methods: Male Balb/c mice (7 weeks) were allowed free access to distilled water (Otsuka Pharmaceutical) containing 2% DSS (molecular weight: 36,000–50,000; ICN Biomedicals) for 6 days to induce colitis. ER-464195-01 (10 mg/kg) or vehicle was orally administered once per day for 6 days. Results: To investigate differentially expressed genes (false discovery rate (FDR) p2) among three groups, we performed pairwise comparisons of RNA-Seq data using the CLC Genomics Workbench software. In comparison with the control, 5,570 (3,483 up- and 2,087 down-regulated) unique genes were significantly changed in the DSS-induced colitis group. Meanwhile, the data set of DSS-induced colitis with ER-464195-01 groups revealed significant changes in 1,808 (837 up- and 971 down-regulated) genes as compared with DSS alone. Notably, of 3,483 genes up-regulated by the DSS treatment, 894 transcripts of which were overlapped with 971 genes down-regulated genes by ER-464195-01. Overall design: Intestinal mRNA profiles of control (normal water), DSS alone and DSS with ER-464195-01 mice were generated by RNA sequencing using the NextSeq 500 (Illumina).