PDF(Pubmed)
Abstract：
Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes-SLC7A11, LRPPRC, NDUFS1, and CD2AP-were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.
摘要：
溃疡性结肠炎（UC）是肠道的慢性炎症状况。肠粘膜中的各种程序性细胞死亡途径对UC的发病机理至关重要。二硫化物下垂，一种最近确定的程序性细胞死亡形式，尚未在UC的背景下广泛报道。这项研究通过公共数据库评估了UC中二硫键沉积相关基因（DRGs）的表达，并通过靶向代谢组学评估了UC患者和葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠的肠粘膜组织中的二硫键积累。我们利用各种生物信息学技术来鉴定UC特异性二硫化物下垂特征基因，分析它们的潜在功能，并探讨其与UC免疫细胞浸润的关系。在DSS诱导的结肠炎小鼠和UC患者的肠粘膜中证实了这些特征基因的mRNA和蛋白质表达水平。总共24个DRGs在UC中显示差异表达。我们的发现强调了二硫键应激在UC中的作用。4个UC相关的二硫键下垂特征基因-SLC7A11,LRPPRC,鉴定了NDUFS1和CD2AP。使用CIBERSORT分析了它们与UC免疫浸润的关系，并通过实时定量PCR和蛋白质印迹法验证其表达水平。这项研究提供了对其潜在功能的进一步见解，并探讨了它们与UC免疫浸润的联系。总之,二硫化物下垂，作为一种程序性细胞死亡，可能通过调节肠粘膜屏障的稳态来显著影响UC的发病机制。
