Relative mRNA expression signature of PBMC-derived NLRP3 inflammasomes in progression of type 2 diabetic kidney disease

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-07-18 DOI:10.1016/j.cyto.2025.156999

Jayashree Kuppuswami , Gandhipuram Periyasamy Senthilkumar , Sreejith Parameswaran , Mehalingam Vadivelan

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引用次数: 0

Abstract

Background

NLRP3 inflammasome triggered by chronic hyperglycemia in resident pro-inflammatory leucocytes of the diabetic kidney is predominant in perpetuating chronic inflammation and renal fibrosis. This study focuses on NLRP3 expressed in circulatory immune cells, to elucidate the systemic level significance of NLRP3 inflammasome in contributing to diabetic kidney disease (DKD) progression. We therefore, aim to investigate the mRNA expression signature of genes encoding the NLRP3 inflammasome complex in circulatory immune cells and its association with severity of DKD in type 2 diabetes mellitus (T2DM) patients.

Materials & methods

PBMCs were isolated from the blood samples of 160 T2DM patients presenting with varying grades of DKD severity. RNA extracted from the PBMCs was used for relative quantification of our target genes using SYBRGreen real-time RT-qPCR. Association of DKD progression with NLRP3 component genes' mRNA expression was analyzed statistically.

Results

Expression of NLRP3, CASP1, and IL1β mRNAs were significantly elevated in DKD; higher HSP72 mRNA expression accompanied normoalbuminuric T2DM. PBMC-derived NLRP3 mRNA levels correlated positively with circulatory monocyte population. Plasma NLRP3 protein and NLRP3 mRNA expressed in PBMCs were associated inversely with decreasing eGFR, independent of diabetes duration, age and sex. Contrastingly, HSP72 mRNA levels declined with decline in eGFR. No association between NLRP3 complex genes and HSP72 mRNA expression in PBMCs was observed, although HSP72 exhibited inverse characteristics to that of NLRP3 complex in the study.

Conclusion

A dynamic interplay exists between DKD progression and PBMC-derived mRNA expression of NLRP3 inflammasome and HSP72. At the systemic level, while NLRP3 exasperates inflammation, the protective role of HSP72 is extinguished. Their expression patterns in circulatory immune cells are associated with eGFR decline, tying systemic inflammatory state to worsening kidney disease outcomes.

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pbmc来源的NLRP3炎症小体在2型糖尿病肾病进展中的相对mRNA表达特征

背景：糖尿病肾中常驻促炎白细胞中由慢性高血糖引发的nlrp3炎性小体在慢性炎症和肾纤维化的持续发展中起主要作用。本研究主要关注NLRP3在循环免疫细胞中的表达，以阐明NLRP3炎性体在糖尿病肾病（DKD）进展中的全身水平意义。因此，我们旨在研究2型糖尿病（T2DM）患者循环免疫细胞中编码NLRP3炎性小体复合物的基因mRNA表达特征及其与DKD严重程度的关系。材料,方法从160例不同DKD严重程度的T2DM患者的血液样本中分离spbmcs。从pbmc中提取的RNA用于SYBRGreen实时RT-qPCR对我们的目标基因进行相对定量。统计学分析DKD进展与NLRP3成分基因mRNA表达的相关性。结果NLRP3、CASP1、il - 1β mrna在DKD中表达显著升高；正常蛋白尿T2DM伴高HSP72 mRNA表达。pbmc衍生的NLRP3 mRNA水平与循环单核细胞数量呈正相关。血浆NLRP3蛋白和NLRP3 mRNA在PBMCs中的表达与eGFR的降低呈负相关，与糖尿病病程、年龄和性别无关。相比之下，HSP72 mRNA水平随着eGFR的下降而下降。NLRP3复合物基因与pbmc中HSP72 mRNA的表达没有关联，尽管HSP72在研究中表现出与NLRP3复合物相反的特征。结论DKD进展与pbmc衍生的NLRP3炎症小体和HSP72 mRNA表达存在动态相互作用。在全身水平上，NLRP3加重炎症，HSP72的保护作用消失。它们在循环免疫细胞中的表达模式与eGFR下降有关，将全身炎症状态与肾脏疾病结果恶化联系起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.