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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\u2013protein 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.<\/jats:p>","DOI":"10.3390\/ijms26073088","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:11:40Z","timestamp":1743135100000},"page":"3088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PTEN: A Novel Diabetes Nephropathy Protective Gene Related to Cellular Senescence"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0610-1864","authenticated-orcid":false,"given":"Kang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shandong Public Health Clinical Center, Shandong University, Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-4565","authenticated-orcid":false,"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"ref_1","unstructured":"GBD Chronic Kidney Disease Collaboration (2020). 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