Peroxisome proliferator-activated receptor α (PPARα) activation has been reported to exert protective effects on podocytes, whereas angiopoietin-like 3 (ANGPTL3) has been shown to exert significant pathogenic effects on these cells. This study aimed to investigate the link between the protective effects of PPARα activation and the pathogenic effects of ANGPTL3 in podocytes. Both PPARα and ANGPTL3 were expressed in cultured podocytes. PPARα mRNA and protein levels decreased whereas ANGPTL3 mRNA and protein levels increased in a time-dependent manner in podocytes treated with puromycin aminonucleoside (PAN). Gemfibrozil, a pharmacological agonist of PPARα, increased PPARα levels and activity in podocytes. The drug also decreased ANGPTL3 levels by potentially weakening ANGPTL3 promoter activity in both normal and PAN-treated podocytes. Furthermore, gemfibrozil significantly decreased PAN-induced apoptosis and F-actin rearrangement. Primary podocytes from Angptl3-knockout mice were cultured. There was no significant difference between Angptl3^−/− podocytes treated with or without gemfibrozil in the lamellipodia numbers after PAN treatment. The results suggested that the protective effects of gemfibrozil on podocytes were not exerted following knockout of the Angptl3 gene. This study identified a novel mechanism of the PPARα agonist gemfibrozil that exerts its protective effects by inhibiting PAN-induced apoptosis and cytoskeleton rearrangements through inhibition of ANGPTL3 expression.

据报道，过氧化物酶体增殖物激活受体 α (PPARα) 激活对足细胞产生保护作用，而血管生成素样 3 (ANGPTL3) 已显示对这些细胞产生显着的致病作用。本研究旨在探讨 PPARα 激活的保护作用与 ANGPTL3 在足细胞中的致病作用之间的联系。无论PPARα和ANGPTL3培养足细胞表达。在用嘌呤霉素氨基核苷 (PAN) 处理的足细胞中，PPARα mRNA 和蛋白质水平降低，而 ANGPTL3 mRNA 和蛋白质水平以时间依赖性方式增加。吉非罗齐是 PPARα 的药理学激动剂，可增加足细胞中 PPARα 的水平和活性。该药物还通过潜在地削弱了 ANGPTL3 水平正常和 PAN 处理的足细胞中的ANGPTL3启动子活性。此外，吉非贝齐显着降低了 PAN 诱导的细胞凋亡和 F-肌动蛋白重排。培养来自Angptl3基因敲除小鼠的原代足细胞。在PAN处理后，用或不用吉非贝齐处理的Angptl3 ^-/-足细胞的片状伪足数量没有显着差异。结果表明，在敲除Angptl3基因后，吉非罗齐对足细胞的保护作用并未发挥。本研究确定了 PPARα 激动剂吉非罗齐的一种新机制，该机制通过抑制ANGPTL3来抑制 PAN 诱导的细胞凋亡和细胞骨架重排，从而发挥其保护作用。 表达。