糖尿病足溃疡愈合中Th1和B细胞以及相关基因表达变化的研究

Changes of Th1 and B cells and related genes in diabetic foot ulcer healing

目的探讨糖尿病足溃疡(DFU)愈合中Th1和B细胞以及相关基因表达的变化。方法选取2022年1月至2023年1月于我院手术治疗的DFU患者皮损组织。从GSE80178和GSE143735中收集DFU相关基因表达数据,鉴定溃疡和非溃疡患者差异表达基因(DEGs)。采用生物信息学方法鉴定溃疡中异常的免疫细胞和关键基因。采用RT-qPCR和流式细胞术检测关键结果。结果2套数据中鉴定548个共同DEGs。在识别的14个共表达模块中,darkgrey和darkgreen与溃疡相关性最高,与酶活性、免疫功能和内分泌调节有关。流式细胞术验证Th1和B细胞在溃疡组织中的高浸润以及治愈溃疡组织中降低。基质金属蛋白酶13(MMP13)、钙结合蛋白A9(S100A9)和信号转导和转录激活因子4(STAT4)参与免疫信号通路,MMP13和STAT4在治愈的DFU中低表达,S100A9高表达。结论Th1和B细胞在治愈的DFU中浸润水平降低,可能参与DFU愈合。

Objective To explore the changes in Th1 cell,B cell and related gene expression during the healing of diabetic foot ulcers(DFU).Methods Lesional skin tissues from DFU patients surgically treated in our hospital from January 2022 to January 2023 were selected.DFU associated gene expression data were collected from GSE80178 and GSE143735 datasets.The expressions of genes(DEGs)between ulcer and no-ulcer patients were identified.Bioinformatics methods were used to identify abnormal immune cells and key genes.Finally,the key results were detected by RT-qPCR and flow cytometry.Results A total of 548 common DEGs were identified in two datasets.In 14 co-expression modules,darkgrey and darkgreen were most related to ulcer,which were mainly associated with the regulation of enzyme activity,immune function and endocrine regulation.Flow cytometry showed that Th1 and B cells were highly infiltrated in ulcer tissue and decreased in healing tissue.MMP13,S100A9 and STAT4 were involved in immune signaling pathways.MMP13 and STAT4 were lowly expressed in healed ulcers,whereas S100A9 was highly expressed.ConclusionReduced levels of Th1 and B cell infiltration may promote DFU healing.