中国病理生理杂志2024，Vol.40Issue(5)：882-889,8.DOI:10.3969/j.issn.1000-4718.2024.05.013
肾小管脂滴包被蛋白2在预测糖尿病肾脏病进展中的作用及机制
Application and mechanism of renal tubular perilipin 2 in predicting de-cline in renal function in diabetic kidney disease patients
摘要
Abstract
AIM: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 explore the potential mechanisms in-volved in renal tubular cell injury induced by PLIN2 during the progression of DKD.METHODS:Control individuals(n=12)and DKD patients(n=51)were enrolled in this retrospective cohort study.Demographic and laboratory data were col-lected.A simplified linear mixed-effects model was applied to assess the estimated glomerular filtration rate(eGFR)slope.The relationship between PLIN2 and renal function decline 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.Western blot-ting and immunofluorescence staining were used to detect PLIN2 expression.Lipid droplets were stained with oil red O.The oxygen consumption rate(OCR)of mitochondria was measured using an extracellular flux analyser.RESULTS:The expression of PLIN2 was markedly higher 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·1.73 m2·year).An in-crease in the baseline percentage of PLIN2-positive tubules was significantly associated with the eGFR slope during the fol-low-up period[hazard ratio(HR)=1.90,95%confidence interval(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.Knockdown of PLIN2 significantly alleviated glucose-in-duced lipid droplet accumulation,whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation.The decrease in mitochondrial OCR in renal tubular cells induced by glucose treatment was alleviated after PLIN2 knock-down.However,overexpression of PLIN2 directly decreased the mitochondrial OCR.CONCLUSION:The PLIN2 ex-pression in tubules predicts a decline in renal function in patients with DKD.The PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD.关键词
糖尿病肾脏病/脂滴包被蛋白2/估算的肾小球滤过率斜率/脂滴/氧消耗率Key words
diabetic kidney disease/perilipin 2/estimated glomerular filtration rate slope/lipid droplet/oxy-gen consumption rate分类
医药卫生引用本文复制引用
沈蕊,于心,石彩凤,秦松言,方奕,何爱琴,吴小梅,杨俊伟,周阳..肾小管脂滴包被蛋白2在预测糖尿病肾脏病进展中的作用及机制[J].中国病理生理杂志,2024,40(5):882-889,8.基金项目
国家自然科学基金资助项目(No.82270760) （No.82270760）
江苏省自然科学基金资助项目(No.BK20201497) （No.BK20201497）
