He Qiong, Wu Xiao-Han, Jiang Dong-Lang, Lin Ri-Tian, Xie Fang, Guan Yi-Hui, Fei Ai-Hua
Department of General Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, Henan Province, China.
World J Gastroenterol. 2025 Jul 21;31(27):109239. doi: 10.3748/wjg.v31.i27.109239.
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact. The exact etiology of this condition remains unclear. Neutrophils play a critical role in IBD pathogenesis. Translocator protein (TSPO), a mitochondrial protein linked to immune responses, has demonstrated potential as an inflammatory marker. However, its role in IBD remains underexplored.
To investigate the role of TSPO in IBD pathogenesis, particularly in neutrophils.
Bioinformatics analyses of Gene Expression Omnibus datasets (GE75214, GSE94648, GSE156776) assessed TSPO expression in IBD patients. TSPO expression was evaluated in human IBD samples, neutrophiles and a chronic colitis mouse model. Neutrophil function was examined in 18 samples using reactive oxygen species (ROS) production and neutrophil extracellular trap (NET) formation assays. Positron emission tomography-computed tomography (PET-CT) imaging and histology from 12 mice revealed TSPO expression in colitis. PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.
Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD, especially in neutrophils. This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining, which showed a significant upregulation of TSPO in active IBD. Neutrophils from patients with UC and CD exhibited higher TSPO expression, which correlated with increased ROS production and NET formation. In a mouse model of dextran sodium sulfate-induced chronic colitis, TSPO was upregulated in the colonic neutrophils and brain tissues, indicating its systemic involvement. PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions, particularly in the microglia, highlighting neuroinflammation.
TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation. Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.
炎症性肠病（IBD），包括溃疡性结肠炎（UC）和克罗恩病（CD），是慢性胃肠道疾病，在全球的患病率不断上升，对医疗保健产生重大影响。这种疾病的确切病因仍不清楚。中性粒细胞在IBD发病机制中起关键作用。转位蛋白（TSPO）是一种与免疫反应相关的线粒体蛋白，已显示出作为炎症标志物的潜力。然而，其在IBD中的作用仍未得到充分研究。
研究TSPO在IBD发病机制中的作用，特别是在中性粒细胞中的作用。
对基因表达综合数据库（GE75214、GSE94648、GSE156776）进行生物信息学分析，评估IBD患者中TSPO的表达。在人类IBD样本、中性粒细胞和慢性结肠炎小鼠模型中评估TSPO表达。使用活性氧（ROS）生成和中性粒细胞胞外陷阱（NET）形成试验检测18个样本中的中性粒细胞功能。12只小鼠的正电子发射断层扫描-计算机断层扫描（PET-CT）成像和组织学检查显示结肠炎中TSPO的表达。PET-CT和免疫荧光染色评估神经炎症条件下大脑中TSPO的表达。
生物信息学分析显示，IBD患者的肠黏膜和外周血中TSPO表达升高，尤其是在中性粒细胞中。定量实时聚合酶链反应和免疫组织化学染色证实了这一点，其显示活动期IBD中TSPO显著上调。UC和CD患者的中性粒细胞表现出较高的TSPO表达，这与ROS生成增加和NET形成相关。在葡聚糖硫酸钠诱导的慢性结肠炎小鼠模型中，结肠中性粒细胞和脑组织中TSPO上调，表明其全身受累。PET-CT成像显示炎症结肠和脑区，特别是小胶质细胞中TSPO摄取增强，突出了神经炎症。
IBD患者中性粒细胞中TSPO显著上调，并导致肠道炎症。其在肠道中的高表达突出了其作为IBD有前景的治疗靶点的潜力。
