Zhou Ying, Fang Xiao, Huang Lin-Jing, Wu Pei-Wen
Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
Department of Kidney Transplantation, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China.
World J Diabetes. 2025 Feb 15;16(2):101538. doi: 10.4239/wjd.v16.i2.101538.
The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome may play an important role in diabetic kidney disease (DKD). However, the exact link remains unclear.
To investigate the role of the NLRP3 inflammasome in DKD.
Using datasets from the Gene Expression Omnibus database, 30 NLRP3 inflammasome-related genes were identified. Differentially expressed genes were selected using differential expression analysis, whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes. Subsequently, three machine learning algorithms were used to screen genes, and biomarkers were identified by overlapping the genes from the three algorithms. Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes.
Two biomarkers, sirtuin 2 (SIRT2) and caspase 1 (CASP1), involved in the Leishmania infection pathway were identified. Both biomarkers were expressed in endothelial cells. Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage. Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group ( < 0.05), and SIRT2 content decreased ( < 0.05).
SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.
NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎性小体可能在糖尿病肾病（DKD）中起重要作用。然而，确切的联系仍不清楚。
研究NLRP3炎性小体在DKD中的作用。
利用基因表达综合数据库中的数据集，鉴定出30个与NLRP3炎性小体相关的基因。使用差异表达分析选择差异表达基因，而基于重叠的差异表达基因和NLRP3炎性小体相关基因选择交集基因。随后，使用三种机器学习算法筛选基因，并通过重叠三种算法的基因来鉴定生物标志物。通过蛋白质印迹法在糖尿病db/db小鼠模型中验证潜在的生物标志物。
鉴定出两个参与利什曼原虫感染途径的生物标志物，即沉默调节蛋白2（SIRT2）和半胱天冬酶1（CASP1）。两种生物标志物均在内皮细胞中表达。基于内皮细胞的伪时间分析表明，DKD大多发生在分化中期。蛋白质印迹结果显示，DKD组中CASP1的表达高于对照组（<0.05），而SIRT2的含量降低（<0.05）。
SIRT2和CASP1为DKD治疗提供了潜在的理论基础。
