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Next Generation Sequencing Facilitates Quantitative Analysis of DSS-induced colitis receiving Sulfasalazine and Berberine colonrectum Transcriptomes

ABSTRACT: Next Generation Sequencing Facilitates Quantitative Analysis of DSS-induced colitis receiving Sulfasalazine and Berberine colonrectum Transcriptomes

PROVIDER: PRJNA892880 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21998782.fastq.gz	Fastqsanger.gz
	SRR21998783.fastq.gz	Fastqsanger.gz
	SRR21998784.fastq.gz	Fastqsanger.gz
	SRR21998785.fastq.gz	Fastqsanger.gz
	SRR21998786.fastq.gz	Fastqsanger.gz

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Project description:Ulcerative colitis (UC) is a life-threatening heterogeneous condition characterized by inflammation of the colon. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is essential for antigen processing and immune regulation, however, its specific role in UC pathogenesis and therapeutic response remains unclear. This study aimed to investigate the role of ERAP1 in the response to sulfasalazine, a standard treatment for UC, using an ERAP1-heterozygous (ERAP1⁺/⁻) mouse model susceptible to colitis. Wild-type (WT) and ERAP1+/− mice were treated with 2.5% dextran sulfate sodium (DSS) to induce colitis, followed by sulfasalazine administration. Colitis severity was assessed through histopathology. Immune cell populations, including neutrophils, dendritic cells, T cells, and NK1.1+ cells, were analyzed using flow cytometry. RNA sequencing of colonic tissues was performed to assess gene expression changes associated with reduced ERAP1 expression. ERAP1+/− mice exhibited more severe DSS-induced colitis, with greater weight loss and increased mucosal damage compared to WT mice. In addition, ERAP1+/− colitis mice showed marked changes in peripheral blood and intestinal intraepithelial lymphocyte (IELs) immune cell infiltration after sulfasalazine treatment. RNA sequencing identified 428 differentially expressed genes between ERAP1⁺/⁻ and WT mice. Among these, 28 genes were previously associated with colitis or colorectal cancer, of which 11 were upregulated and 17 downregulated in ERAP1⁺/⁻ mice. RT-qPCR analysis further confirmed that the expression of Anxa9, Atp2a1, and Hepacam2 was significantly elevated in ERAP1⁺/⁻ mice following sulfasalazine treatment, suggesting a differential therapeutic response. Collectively, our study demonstrates that partial ERAP1 deficiency exacerbates DSS-induced colitis by promoting immune dysregulation and altering the expression of inflammation-related genes. These findings suggest that reduced ERAP1 expression may impair the therapeutic efficacy of sulfasalazine. Therefore, ERAP1 may serve as a key regulator in the pathogenesis of UC and a potential target for therapy.

Project description:Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functional role of miRNAs in murine models of colitis facilitates elucidating the role of specific miRNAs in human IBD. The aim of this study was to determine the miRNA signature of murine models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miRNAs expression was accessed by microarray for acute and chronic murine model of colitis induced by DSS or TNBS. miR-21-deficient mouse and littermates controls were assessed in the standard DSS, TNBS and CD4+ T cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative RT-PCR. Th1 polarization was accessed by flow-cytometry and ELISA. Results: Alterations of in miRNAs expression were identified for acute and chronic DSS colitis and TNBS colitis, receptively. The Expression of miRs-21, -142-3p and -223 was were distinct between DSS and TNBS models while overlap of numerous miRNAs was seen. Importantly, miRs-19b, -192 and -215, that are decreased in IBD, were significantly decreased in all 4 models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis but not the DSS colitis models. Further assessment of the miR-21-deficient 1-/- mice revealed that the deletion of miR-21 results in the exacerbation of both the TNBS and T cell-transfer models of colitis. Conclusions: miRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T cell-mediated models of colitis provides further evidence that miRNAs play significant roles in the pathogenesis of IBD. miRNAs expression was accesed for acute and chronic murine model of colitis induced by DSS or TNBS.Total of 20 samples with duplicates were analyed in this study.

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Next Generation Sequencing Facilitates Quantitative Analysis of DSS-induced colitis receiving Sulfasalazine and Berberine colonrectum Transcriptomes

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