Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats
Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats
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DOI：
10.1681/asn.2006070710
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发表时间：
2007-05-01
影响因子：
13.6
通讯作者：
Yap, Hui-Kim
中科院分区：
文献类型：
--
作者：
Lai, Kin-Wai;Wei, Chang-Li;Yap, Hui-Kim
IL-13参与了微小病变型肾病综合征的发病机制。本研究旨在探讨IL-13在蛋白尿发生和肾病综合征相关足细胞相关基因表达中的作用。通过体内电穿孔将克隆有大鼠IL-13基因的哺乳动物表达载体导入Wistar大鼠的股四头肌，在Wistar大鼠体内过表达IL-13。连续检测血清IL-13、白蛋白、胆固醇、肌酐和尿白蛋白。第70天后取肾脏进行组织学和电子显微镜观察。用实时荧光定量聚合酶链式反应检测肾小球组织中newitin、podocin、dystroglan、B7-1和IL-13受体亚基的基因表达，并将其作为抗β-肌动蛋白的指标。免疫荧光染色检测这些分子的蛋白表达。与对照组(n=17)相比，IL-13转基因大鼠(n=41)出现明显的蛋白尿、低蛋白血症和高胆固醇血症。IL-13转基因大鼠肾小球未见明显的组织学改变。然而，电子显微镜显示高达80%的足细胞足突融合。肾小球B7-1、IL-4Rα和IL-13Rα2基因表达显著上调，而neparin、podocin和dystroglan基因表达下调。与对照组相比，IL-13转染组大鼠脑啡肽、podocin和营养不良多糖的免疫荧光染色强度降低，而B7-1和11，4Rα的免疫荧光染色强度增加。综上所述，这些结果表明，IL-13在大鼠体内的过度表达可导致足细胞损伤，同时肾小球中neparin、podocin和dystroglan下调，同时B7-1上调，导致以蛋白尿增加、低蛋白血症、高胆固醇血症和足细胞足突融合为特征的轻微变化样肾病。
IL-13 has been implicated in the pathogenesis of minimal-change nephrotic syndrome. This study aimed to investigate the role of IL-13 on the development of proteinuria and expression of podocyte-related genes that are associated with nephrotic syndrome. IL-13 was overexpressed in Wistar rats through transfection of a mammalian expression vector cloned with the rat IL-13 gene, into the quadriceps by in vivo electroporation. Serum IL-13, albumin, cholesterol, and creatinine and urine albumin were measured serially. Kidneys were harvested after day 70 for histology and electron microscopy. Glomerular gene expression of nephrin, podocin, dystroglycan, B7-1, and IL-13 receptor subunits were examined using real-time PCR with hybridization probes and expressed as an index against beta-actin. Protein expression of these molecules was determined by immunofluorescence staining. The IL-13-transfected rats (n = 41) showed significant albuminuria, hypoalbuminemia, and hypercholesterolemia when compared with control rats (n = 17). No significant histologic changes were seen in glomeruli of IL-13-transfected rats. However, electron microscopy showed up to 80% of podocyte foot process fusion. Glomerular gene expression was significantly upregulated for B7-1, IL-4R alpha, and IL-13R alpha 2 but downregulated for nephrin, podocin, and dystroglycan. Immunofluorescence staining intensity was reduced for nephrin, podocin, and dystroglycan but increased for B7-1 and 11,4R alpha in IL-13-transfected rats compared with controls. In conclusion, these results suggest that IL-13 overexpression in the rat could lead to podocyte injury with downregulation of nephrin, podocin, and dystroglycan and a concurrent upregulation of B7-1 in the glomeruli, inducing a minimal change-like nephropathy that is characterized by increased proteinuria, hypoalbuminemia, hypercholesterolemia, and fusion of podocyte foot processes.