Abstract
Ulcerative colitis (UC) is a complex inflammatory bowel disorder that can induce colonic and rectal dysfunction. Mesalazine, a first-line medicine, is routinely prescribed for UC treatment. However, the pharmacological targets of mesalazine against UC are not detailed in current publications. In the current study, a transcriptomics strategy was applied to reveal the therapeutic targets and molecular mechanisms of mesalazine for treating dextran sulfate sodium (DSS)-induced UC in mice. Compared with the UC group, a total of 1,663 differentially expressed genes were identified in mesalazine-treated mice, of which 262 were upregulated and 1,401 were downregulated. GO and KEGG enrichment analyses indicated that the protective actions of mesalazine for treating UC were related to the functional regulation of immune inflammatory response, such as the regulation of T cells, white blood cells, and cytokine receptor pathways. In addition, ingenuity pathway analysis of the gene network further revealed the inhibitory action of mesalazine on C–C motif chemokine ligands (CCL11 and CCL21) and C–X–C motif chemokine ligands (CXCL3 and CXCR2). Taken together, the current transcriptomic findings revealed anti-UC pharmacological targets, including the newly discovered biotargets CCL11, CCL21, CXCL3, and CXCR2, of mesalazine against DSS-induced intestinal inflammation.
Highlights
Ulcerative colitis (UC), a refractory enteritis disease, is characterized by mucosal inflammation and enterocyte lesions present in the gastrointestinal tract (Guan, 2019)
We performed comparative transcriptomic analysis to understand the molecular basis of dextran sulfate sodium (DSS)-induced colitis
It has been well reported that the major cause of UC results from abnormal immune responses to antigens derived from the intestinal microbiota (Podolsky, 2002; Macdonald and Monteleone, 2005)
Summary
Ulcerative colitis (UC), a refractory enteritis disease, is characterized by mucosal inflammation and enterocyte lesions present in the gastrointestinal tract (Guan, 2019). It is reported that the prevalence and burden of UC are increasing worldwide, including in China (Ordás et al, 2012). Environmental factors, and dietetic alterations may be crucial risk indicators. Chronic UC in Asian patients may result in an elevated risk of developing colorectal cancer when compared with that of the general population (Bopanna et al, 2017). The pathological etiology of UC is multifaceted, including impaired barrier function in the mucus layer, lamina propria lesion, gut microbiota imbalance, and neutrophilic immune response (Kobayashi et al, 2020). Treat-to-target, a countermeasure used for treating chronic disorders, may be achieved by determining pathological targets and mitigating UC (Ungaro et al, 2019)
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