Transcriptome and single-cell profiling of the mechanism of diabetic kidney disease.

IF 4.6 3区医学 Q1 ENDOCRINOLOGY & METABOLISM World Journal of Diabetes Pub Date : 2025-02-15 DOI:10.4239/wjd.v16.i2.101538

Ying Zhou, Xiao Fang, Lin-Jing Huang, Pei-Wen Wu

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Abstract

Background: 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.

Aim: To investigate the role of the NLRP3 inflammasome in DKD.

Methods: 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.

Results: 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 (P < 0.05), and SIRT2 content decreased (P < 0.05).

Conclusion: SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.

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糖尿病肾病机制的转录组和单细胞谱分析。

背景：nod样受体热蛋白结构域相关蛋白3 （NLRP3）炎症小体可能在糖尿病肾病（DKD）中发挥重要作用。然而，确切的联系尚不清楚。目的：探讨NLRP3炎性体在DKD中的作用。方法：利用基因表达综合数据库的数据集，鉴定30个NLRP3炎症小体相关基因。通过差异表达分析选择差异表达基因，通过重叠差异表达基因和NLRP3炎性小体相关基因选择交叉基因。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中的基因来识别生物标记物。在db/db糖尿病小鼠模型中，通过western blotting验证了潜在的生物标志物。结果：鉴定出参与利什曼原虫感染途径的两种生物标志物sirtuin 2 （SIRT2）和caspase 1 （CASP1）。这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显示，DKD主要发生在分化中期。Western blotting结果显示，DKD组CASP1表达高于对照组（P < 0.05）， SIRT2含量降低（P < 0.05）。结论：SIRT2和CASP1为DKD的治疗提供了潜在的理论基础。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.