PLK2 contributes to autophagic dysfunction and tubular injury in diabetic kidney disease

Diabetic kidney disease (DKD) is characterized by progressive tubulointerstitial injury, in which autophagy dysfunction contributes to renal damage. Polo-like kinase 2 (PLK2) has been implicated in autophagy regulation, but its role in DKD remains unclear. This study aimed to identify autophagy-related biomarkers and determine the clinical and functional relevance of PLK2 in DKD. Four DKD-related GEO datasets were integrated with 803 autophagy-related genes. Functional enrichment, protein–protein interaction analysis, LASSO, and SVM-RFE were used to identify candidate genes. PLK2 expression and clinicopathological associations were evaluated in renal biopsy specimens from 51 DKD patients, 6 normal controls, and 15 minimal change disease patients. High-glucose-treated HK-2 cells were subjected to PLK2 knockdown, Western blotting, bafilomycin A1-mediated autophagic-flux analysis, CCK-8 assays, and Annexin V/PI flow cytometry. Eleven autophagy-related differentially expressed genes were identified, and PLK2 emerged as a key candidate. The four-gene diagnostic model achieved AUCs of 0.979 and 0.884 in the training and testing sets, respectively. PLK2 was increased in DKD kidneys and associated with p62, NGAL, tubular injury markers, and IFTA severity, while negatively correlating with eGFR. PLK2 was independently associated with moderate-to-severe IFTA. In HK-2 cells, PLK2 knockdown reduced p62 accumulation and tubular injury markers, improved viability, attenuated apoptosis, and partially restored autophagic flux under high-glucose conditions. PLK2 is closely associated with autophagic dysfunction and tubulointerstitial injury in DKD. These findings support PLK2 as a candidate biomarker and potential therapeutic target.