Volume 10,Issue 1
Fall 2025
Application and Mechanism of Renal Tubular Perilipin 2 in Predicting Decline in Renal Function in Diabetic Kidney Disease Patients
Objective: To investigate whether changes in the expression of perilipin 2 (PLIN2) in renal tubular epithelial cells can predict the decline in renal function in diabetic kidney disease (DKD) and to elucidate the mechanism by which PLIN2 promotes tubular epithelial cell damage in DKD. Methods: A retrospective cohort study was conducted involving 12 non-diabetic patients (as controls) and 51 DKD patients. Demographic data and laboratory test results were collected. A simplified linear mixed-effects model was used to calculate the estimated glomerular filtration rate (eGFR) slope. The relationship between PLIN2 and renal function decline in DKD patients was analyzed using Spearman correlation and generalized linear models. In vivo experiments employed BKS-db/db mice and streptozotocin-induced diabetic mouse models. In vitro experiments used primary renal tubular epithelial cells treated with glucose, transfected with PLIN2 siRNA, or overexpressing PLIN2 plasmids. Protein immunoblotting and immunofluorescence staining were used to detect PLIN2 expression. Oil Red O staining assessed lipid droplet accumulation and a real-time cellular metabolic analyzer measured mitochondrial oxygen consumption rate (OCR). Results: The expression level of PLIN2 in renal tubules was significantly elevated in DKD patients compared to controls. Over a follow-up period of 24 (12, 39) months, the eGFR slope in DKD patients was -7.42 (-19.77, -2.09) mL/(min·1.73 m²·year). The baseline percentage of PLIN2-positive area in renal tubules was significantly associated with changes in the eGFR slope during follow-up hazard ratio (HR) = 1.90, 95, suggesting the predictive value of tubular PLIN2 for renal function decline in DKD. Diabetic mouse models exhibited significantly increased lipid droplet accumulation and PLIN2 expression in renal tubules compared to controls. In vitro, glucose treatment induced lipid droplet accumulation and increased PLIN2 expression in renal tubular epithelial cells. PLIN2 knockdown significantly alleviated glucose-induced lipid droplet accumulation, while PLIN2 overexpression exacerbated it. The decline in mitochondrial OCR caused by glucose treatment was mitigated by PLIN2 knockdown, whereas PLIN2 overexpression directly reduced mitochondrial OCR. Conclusion: PLIN2 in renal tubules can predict renal function decline in DKD patients. PLIN2 inhibits mitochondrial oxidative respiration, promotes lipid droplet accumulation in renal tubular epithelial cells, and contributes to the progression of DKD.
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