Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The current diagnostic and therapeutic approaches need to be improved. Cellular senescence has been implicated in the pathogenesis of DN, but its precise role remains unclear. This study aimed to identify key pathogenic genes related to cellular senescence in DN and explore their potential as diagnostic biomarkers. Using transcriptomic data from GEO datasets (GSE96804, GSE30122, GSE142025, and GSE104948) and cellular senescence-related genes sourced from the GenAge database, we integrated multiple bioinformatics approaches, including differential expression analysis, weighted gene co-expression network analysis (WGCNA), machine learning and protein-protein interaction (PPI), to identify diagnostic genes. PTEN was identified as a key diagnostic gene. Immune infiltration analysis revealed that PTEN expression is positively correlated with macrophage M2 and dendritic cell resting infiltration and negatively correlated with monocytes and neutrophils. snRNA analysis revealed that PTEN is mainly expressed in mesangial cells. Finally, RT-PCR results revealed that the mRNA expression of PTEN was upregulated in kidneys from db/db mice. Additionally, high-glucose treatment significantly upregulated PTEN expression in cultured human mesangial cells. This study identifies PTEN as a potential diagnostic biomarker for DN which may contribute to early detection and personalized therapeutic strategies.