Investigation of TNF and related lncRNAs in diabetic nephropathy

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-18 DOI:10.1016/j.cyto.2025.156892

Seyed Mohsen Aghaei-Zarch , Leila Mahmoudieh , Mohammad Miryounesi , Maryam Aghazadeh , Mehran Reihani-Ardabili , Marzieh Zamani , Marzieh Motallebi , Abolfazl Movafagh

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引用次数: 0

Abstract

Background

Diabetic nephropathy (DN) is a significant driver of end-stage renal disease, requiring kidney replacement therapies such as transplantation and dialysis. Given the critical importance of understanding the onset and progression of DN, we sought to explore the expression levels of tumor necrosis factor (TNF) and related long noncoding RNAs (lncRNAs) in diabetic patients with and without DN, as well as in pre-diabetic individuals, compared to healthy controls. We further explored the involvement of TNF and TNF-related lncRNAs in high glucose (HG)-induced apoptosis of human embryonic kidney (HEK)-293 cells.

Material and method

In the current cross-sectional investigation, we compare the expression levels of lncRNA myocardial infarction-associated transcript (MIAT), lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and TNF in 50 healthy individuals, 50 people with prediabetes, 50 patients with type 2 diabetes mellitus (T2DM), and 50 patients with T2DM- DN. We cultured HEK293 cells in a HG condition (100 mM glucose) to establish a cellular model of DN, while HEK293 cells cultured in a normal-glucose environment (5 mM glucose) served as controls. We further assess apoptosis in HEK293 cells via flow cytometry analysis. Moreover, we evaluated the expression levels of lncRNA MIAT, lncRNA NEAT1, and TNF in HG and normal-glucose (NG) groups to investigate their potential involvement in HEK293 cell apoptosis and the pathogenesis of DN.

Result

Our findings reveal a significant upregulation of lncRNA MIAT, lncRNA NEAT1, and TNF in T2DM and T2DM-associated DN groups compared to prediabetic individuals and healthy controls (p < 0.05). Furthermore, HG conditions significantly increased the apoptotic rate of HEK293 cells. Additionally, the expression levels of TNF, lncRNA MIAT, and lncRNA NEAT1 were increased in HEK-293 cells cultured in a HG.

Conclusion

In conclusion, our findings indicate a significant role for the TNF gene and associated lncRNAs, such as lncRNA MIAT and lncRNA NEAT1, in podocyte apoptosis and the development of DN.

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糖尿病肾病中TNF及相关lncrna的研究

糖尿病肾病（DN）是终末期肾脏疾病的重要驱动因素，需要肾脏替代治疗，如移植和透析。鉴于了解DN的发病和进展至关重要，我们试图探索与健康对照相比，有DN和无DN的糖尿病患者以及糖尿病前期个体中肿瘤坏死因子（TNF）和相关长链非编码rna （lncRNAs）的表达水平。我们进一步探讨了TNF和TNF相关lncrna在高糖（HG）诱导的人胚胎肾(HEK)-293细胞凋亡中的作用。材料和方法在当前的横断面研究中，我们比较了50名健康个体、50名糖尿病前期患者、50名2型糖尿病（T2DM）患者和50名T2DM- DN患者中lncRNA心肌梗死相关转录物（MIAT）、lncRNA核旁斑组装转录物1 （NEAT1）和TNF的表达水平。我们在HG （100 mM葡萄糖）条件下培养HEK293细胞建立DN细胞模型，而在正常葡萄糖环境（5 mM葡萄糖）培养HEK293细胞作为对照。我们通过流式细胞术分析进一步评估HEK293细胞的凋亡。此外，我们还评估了lncRNA MIAT、lncRNA NEAT1和TNF在HG和正常葡萄糖（NG）组中的表达水平，以探讨它们在HEK293细胞凋亡和DN发病机制中的潜在参与。结果T2DM和T2DM相关DN组中lncRNA MIAT、lncRNA NEAT1和TNF与糖尿病前期和健康对照组相比显著上调(p <；0.05)。此外，HG条件显著增加HEK293细胞的凋亡率。在hg培养的HEK-293细胞中，TNF、lncRNA MIAT和lncRNA NEAT1的表达水平升高。结论TNF基因及其相关lncRNA MIAT和lncRNA NEAT1在足细胞凋亡和DN的发生中发挥了重要作用。

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.