Expression of Angiopoietin-Like 3 Associated with Puromycin-Induced Podocyte Damage
Expression of Angiopoietin-Like 3 Associated with Puromycin-Induced Podocyte Damage
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血管生成素样 3 的表达与嘌呤霉素诱导的足细胞损伤相关
DOI：
10.1159/000313829
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Hao Chuanming
中科院分区：
文献类型：
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作者：
Rao Jia;Xu Hong;Hao Chuanming
血管生成素样蛋白3(Angiopoietin-like 3，Angptl3)是血管生成素家族的一种分泌型蛋白，参与血管生成和脂质代谢的调节。然而，关于Angptl3在肾脏损伤中的作用的数据很少。我们最近报道了血管紧张素转换酶3在阿霉素肾病大鼠肾小球中的分布。在本文中，我们报道了Angptl3在小鼠足细胞中的体外表达。Western印迹和RT-PCR分析显示，嘌呤霉素诱导的足细胞损伤表现为Angptl3呈时间依赖性上调，而Perlecan和agrin的表达呈时间依赖性下调。此外，基因转染后Angptl3的表达增加，足细胞中Perlecan和agrin的表达上调。免疫双标记法显示，pcDNA3.1-Angptl3转染后，Perlecan和Angptl3共定位于足细胞。为了探讨Angptl3基因如何调节嘌呤霉素对足细胞的影响，我们比较了未处理的足细胞和Angptl3基因转染的足细胞的细胞粘附性。Angptl3基因转染组可明显改善嘌呤霉素诱导的足细胞脱离。总之，在嘌呤霉素诱导的足细胞损伤中，Angptl3的表达上调，并与perlecan和agrin的表达减少有关。
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.