Related Experiment Video
Updated: May 27, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Investigation of TNF and related lncRNAs in diabetic nephropathy
Seyed Mohsen Aghaei-Zarch1, Leila Mahmoudieh2, Mohammad Miryounesi1
1Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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.
