Upregulation of nestin, vimentin, and desmin in rat podocytes in response to injury

Upregulation of nestin, vimentin, and desmin in rat podocytes in response to injury
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DOI:
10.1007/s00428-005-0134-9
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发表时间:
2006-04-01
期刊:
影响因子:
3.5
通讯作者:
Yamamoto, T
Yamamoto, T
中科院分区:
医学3区
文献类型:
--
作者:
Zou, J;Yaoita, E;Yamamoto, T

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肾小球足细胞表达上皮细胞不寻常的中间丝(IF)蛋白。为了深入了解IF蛋白在足细胞中的作用,我们研究了巢蛋白、波形蛋白和结蛋白在嘌呤霉素氨基糖苷(PAN)肾病中的表达。巢蛋白,波形蛋白,结蛋白的蛋白质印迹分析表明,它们的专属表达在肾小球,并显示其在肾病肾小球的表达增加。免疫定位研究表明,巢蛋白和波形蛋白主要位于足细胞在正常和肾病肾小球和增强结蛋白染色只发生在足细胞。核糖核酸酶保护试验显示正常肾小球中波形蛋白和巢蛋白表达水平较高,肾病肾小球中所有三种IF转录物均上调。然而,在PAN注射后一天,发现波形蛋白的转录物已经显著增加,而巢蛋白或结蛋白的转录物没有显示出这种增加。这些研究结果表明,足细胞表达三种IF蛋白,即波形蛋白,结蛋白和巢蛋白,这是差异调节响应损伤。IF蛋白的上调可以增加细胞的机械稳定性,从而使足细胞在张力肾小球毛细血管壁上经历形态学变化。
Podocytes in the renal glomerulus express unusual intermediate filament (IF) proteins for epithelial cells. To gain insight into the role of IF proteins in podocytes, we investigated the expression of nestin, vimentin, and desmin in puromycin aminonucleoside (PAN) nephrosis. A Western blot analysis for nestin, vimentin, and desmin demonstrated their exclusive expression in glomeruli and showed their increase in expression in nephrotic glomeruli. Immunolocalization studies showed nestin and vimentin to be located predominantly in the podocytes in both normal and nephrotic glomeruli and that enhancement of desmin staining only occurred in podocytes. A ribonuclease protection assay showed high levels of vimentin and nestin expression in normal glomeruli and an upregulation of all three IF transcripts in nephrotic glomeruli. One day after the PAN injection, however, the vimentin transcripts were found to already have significantly increased, whereas those of nestin or desmin showed no such increase. These findings indicate that podocytes express three IF proteins, namely, vimentin, desmin, and nestin, which are differentially regulated in response to injury. An upregulation of IF proteins may increase the mechanical stability of cells, thus enabling podocytes to undergo morphological changes on the tensile glomerular capillary wall.