Abstract
Ulcerative colitis (UC) is a recurrent, chronic intestinal disease that is currently incurable. Its pathogenesis remains to be further understood. Therefore, seeking new biomarkers and potential drug targets is urgent for the effective treatment of UC. In this study, the gene expression profile GSE38713 was obtained from the GEO (Gene Expression Omnibus) database. Data normalisation and screening of the differentially expressed genes (DEGs) were conducted using R software, and gene ontology (GO) enrichment was performed using Metascape online tools. The PubMed database was used to screen new genes that have not been reported, and SERPINA3 was selected. The correlation between SERPINA3 and other inflammatory factors was analysed by Spearman correlation analysis. Finally, colitis model mice and an in-vitro model were established to validate the function of the SERPINA3 gene. SERPINA3 gene expression was markedly increased in UC patient samples, colitis models and in-vitro models and showed an association with other inflammatory factors. ROC analysis indicated that SERPINA3 could represent a potential biomarker of active UC. Additionally, silencing SERPINA3 in an in-vitro intestinal epithelial inflammatory model significantly decreased the mRNA level of inflammatory factors. This study provides supportive evidence that SERPINA3 may act as a key biomarker and potential drug target in UC treatment.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disorder [1] characterised by manifestations such as rectal bleeding, diarrhoea, abdominal pain, anaemia, and loss of body weight, which seriously attenuates the quality of life of patients [2,3]
This study indicates that SERPINA3 is a new potential biomarker and therapeutic target of UC
Previous studies have shown that the degradation and formation of extracellular matrix are associated with intestinal damage during inflammation, indicating that extracellular matrix may play a critical role in the pathology of UC, which arouses our interest in exploring whether we will be able to find a new gene related to UC in this gene ontology (GO) term
Summary
Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disorder [1] characterised by manifestations such as rectal bleeding, diarrhoea, abdominal pain, anaemia, and loss of body weight, which seriously attenuates the quality of life of patients [2,3]. Long-term or even indefinite drug maintenance therapy imposes a substantial economic burden on patients [4]. The major pharmacological therapies for UC include corticosteroids, anti-inflammatory agents, and biologics [6]. Anti-inflammatory agents, such as 5-aminosalycerates (5-ASAs), have been the mainstay for the treatment of mild-to-moderate UC [7]. 5-ASAs are safe, their prolonged administration causes many side effects, such as headache, diarrhoea, nausea, interstitial nephritis, and hepatitis [8,9]. Corticosteroids are the mainstay of treatment for moderate to severe forms of UC [10]. A proportion of patients do not respond to biologics therapy or become intolerant or lose benefits [14,15,16]. Biologics are expensive, causing a tremendous economic burden for patients and medical care systems [17]. Identification of the key upstream regulatory gene is warranted for UC treatment
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