Huang Hua, Yan Shuai, Guo Tianwei, Hua Qiuwen, Wang Yongtong, Xu Shanshan, Ji Lijiang
Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, Jiangsu Province, China.
Department of Anorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215000, Jiangsu Province, China.
Heliyon. 2024 Jul 14;10(14):e34352. doi: 10.1016/j.heliyon.2024.e34352. eCollection 2024 Jul 30.
The bile acids (BA) in the intestine promote inflammation by interacting with immune cells, playing a crucial role in the progression of UC, but the specific mechanism between the two remains elusive. This study aims to explore the relationship between BAMand UC inflammation and determine its potential mechanisms.Firstly, we employed a hybrid approach using Lasso regression and support vector machine (SVM) feature selection in bioinformatics to identify genes linked to UC and BAM. The relationship between these genes and immune infiltration was explored, along with their correlation with immune factors in the Tumor-Immune System Interaction Database (TISIDB) database. Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis was then used to predict signaling pathways associated with key genes in UC. Single-cell data from the GSE13464 dataset was also analyzed. Finally, Five differentially expressed genes (DEGs) related to BAM (APOA1, AMACR, PEX19, CH25H, and AQP9) were significantly upregulated/downregulated in UC immune cells. The expression of important genes in UC tissue was confirmed in the experimental validation section and AQP9, which showed significant differential expression, was chosen for further validation. The results showed that the AQP9 gene may regulate the IFN - γ/JAK signaling axis, thereby promoting CD8+T cell activation. This research has greatly advanced our comprehension of the pathogenesis and underlying mechanism of BAM in immune cells linked to UC.
肠道中的胆汁酸（BA）通过与免疫细胞相互作用促进炎症，在溃疡性结肠炎（UC）的进展中起关键作用，但两者之间的具体机制仍不清楚。本研究旨在探讨胆汁酸代谢（BAM）与UC炎症之间的关系，并确定其潜在机制。首先，我们采用了一种混合方法，在生物信息学中使用套索回归和支持向量机（SVM）特征选择来识别与UC和BAM相关的基因。探讨了这些基因与免疫浸润之间的关系，以及它们与肿瘤-免疫系统相互作用数据库（TISIDB）中免疫因子的相关性。然后使用基因集富集分析（GSEA）通路富集分析来预测与UC关键基因相关的信号通路。还分析了来自GSE13464数据集的单细胞数据。最后，与BAM相关的五个差异表达基因（DEG）（载脂蛋白A1、α-甲基酰基辅酶A消旋酶、过氧化物酶体生物合成因子19、胆固醇25-羟化酶和水通道蛋白9）在UC免疫细胞中显著上调/下调。在实验验证部分证实了UC组织中重要基因的表达，并选择了显示出显著差异表达的水通道蛋白9进行进一步验证。结果表明，水通道蛋白9基因可能调节干扰素-γ/Janus激酶信号轴，从而促进CD8+T细胞活化。这项研究极大地推进了我们对与UC相关的免疫细胞中BAM的发病机制和潜在机制的理解。
