Application and Mechanism of Renal Tubular Perilipin 2 in Predicting the Decline in Kidney Function in Patients with Diabetic Kidney Disease

Background: To investigate whether the expression of perilipin 2 (PLIN2) in renal tubular cells could predict a decline in renal function in diabetic kidney disease (DKD) patients and to determine the potential mechanisms involved in renal tubular cell injury induced by PLIN2 during the progression of DKD. Methods: Control individuals and DKD patients were enrolled in this retrospective cohort study. The relationship between expression of PLIN2 in kidney tubules and estimated glomerular filtration rate (eGFR) slope in DKD patients was predicted by Spearman correlation analysis and a generalized linear model. BKS-db/db diabetic mice and streptozotocin-induced diabetic mice were used. Primary renal tubular cells were treated with glucose and transfected with small interfering RNA or plasmid. Results: The expression of PLIN2 was markedly greater in the tubules of DKD patients than in those of control subjects. After 24 (12, 39) months of follow-up, the eGFR slope of DKD patients was -7.42 (-19.77, -2.09) ml/min/1.73m2/year. An increase in the baseline percentage of PLIN2-positive tubules was significantly associated with a change in the eGFR slope during the follow-up period (HR = 1.90, 95% CI: 1.00~3.58), indicating that tubular PLIN2 could predict a decrease in renal function in DKD patients. Both the accumulation of lipid droplets and the expression of PLIN2 were markedly greater in the tubules of diabetic mice than in those of control mice. Glucose treatment induced lipid droplet accumulation and PLIN2 expression in renal tubular cells. PLIN2 deficiency significantly alleviated glucose-induced lipid droplet accumulation, whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation. The decrease in mitochondrial oxygen consumption rate (OCR) in renal tubular cells induced by glucose treatment was alleviated after PLIN2 interference. However, overexpression of PLIN2 directly decreased the mitochondrial OCR. Conclusion: PLIN2 expression in tubules predicts a decline in renal function in patients with DKD. PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD. Funding: Government Support – Non-U.S.