上睑下垂
溃疡性结肠炎
转录组
坏死性下垂
裂谷1
内部收益率1
基因
结肠炎
生物
计算生物学
基因表达
炎症体
细胞凋亡
医学
免疫学
炎症
疾病
程序性细胞死亡
遗传学
内科学
作者
Jun-Meng Wang,Jicheng Yang,Wei Xia,Yue-Mei Wang,Yuanbing Zhu,Qin Huang,Tao Feng,Lushuang Xie,Sihui Li,Shuqing Liu,Shu-Guang Yu,Qiaofeng Wu
摘要
Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.
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