Department of Nephrology, Children's Hospital of Fudan University, Shanghai, People's Republic of China.
Nephron Exp Nephrol. 2010;115(3):e38-45. doi: 10.1159/000313829. Epub 2010 Apr 24.
Angiopoietin-like 3 (ANGPTL3) is a secreted protein of the angiopoietin family and is involved in angiogenesis and lipid metabolism regulation. However, there is little data regarding the role of ANGPTL3 in kidney injury. We recently reported the glomerular distribution of ANGPTL3 in Adriamycin nephropathy in rats. In the present paper, we report expression of ANGPTL3 by murine podocytes in vitro. Puromycin-induced injury of cultured podocytes showed a time-dependent upregulation of ANGPTL3 accompanied by a time-dependent downregulation of perlecan and agrin by Western blot and RT-PCR analysis. In addition, the increased expression of ANGPTL3 following gene transfection upregulated the expression of perlecan and agrin in podocytes. Double immunolabeling demonstrated colocalization of perlecan and ANGPTL3 on podocytes following pcDNA3.1-ANGPTL3 transfection. To explore how ANGPTL3 transfection modulates the effect of puromycin on podocytes, we compared cell adhesion in untreated podocytes and ANGPTL3-transfected podocytes. ANGPTL3 gene transfection significantly ameliorated puromycin-induced podocyte detachment. In conclusion, ANGPTL3 expression is upregulated in puromycin-induced podocyte damage and is associated with the reduction of perlecan and agrin expression.
血管生成素样蛋白 3（ANGPTL3）是血管生成素家族的一种分泌蛋白，参与血管生成和脂质代谢调节。然而，关于 ANGPTL3 在肾脏损伤中的作用的数据很少。我们最近报道了 ANGPTL3 在阿霉素肾病大鼠肾小球中的分布。在本研究中，我们报告了体外培养的小鼠足细胞中 ANGPTL3 的表达。嘌呤霉素诱导的培养足细胞损伤通过 Western blot 和 RT-PCR 分析显示 ANGPTL3 的表达呈时间依赖性上调，伴随硫酸乙酰肝素蛋白聚糖和聚集蛋白的时间依赖性下调。此外，基因转染后 ANGPTL3 的表达增加上调了足细胞中硫酸乙酰肝素蛋白聚糖和聚集蛋白的表达。双重免疫标记显示，pcDNA3.1-ANGPTL3 转染后足细胞上硫酸乙酰肝素蛋白聚糖和 ANGPTL3 共定位。为了探讨 ANGPTL3 转染如何调节嘌呤霉素对足细胞的影响，我们比较了未经处理的足细胞和 ANGPTL3 转染的足细胞的细胞黏附。ANGPTL3 基因转染显著改善了嘌呤霉素诱导的足细胞脱落。总之，嘌呤霉素诱导的足细胞损伤中 ANGPTL3 的表达上调，并与硫酸乙酰肝素蛋白聚糖和聚集蛋白表达的减少相关。
