Nephrin is involved in podocyte maturation but not survival during glomerular development
Nephrin is involved in podocyte maturation but not survival during glomerular development
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DOI：
10.1038/sj.ki.5002707
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发表时间：
2008-03-01
影响因子：
19.6
通讯作者：
Tryggvason, K.
中科院分区：
文献类型：
--
作者：
Done, S. C.;Takemoto, M.;Tryggvason, K.
去氧肾上腺素是肾小球裂隙隔膜 (SD) 的主要成分，它既是一种结构蛋白，也是一种信号分子，影响足突 (FP) 的形成和足细胞完整性的维持。对近期胚胎肾脏的分析显示，去氧肾上腺素敲除小鼠的肾小球细胞活力正常，并且没有细胞凋亡。此外，野生型和突变型小鼠中其他 SD 或肾小球基底膜成分的表达和位置相似，大多数足细胞特异性蛋白的位置和水平也相似。转录谱显示，去氧肾上腺素的缺乏对 FP 和 SD 蛋白基因的表达影响较小。 Claudin 3 是一种紧密连接蛋白，通常在肾小球中不存在，但在基因敲除小鼠中，其表达上调三倍，这表明去氧肾上腺素在肾小球内 Claudin 3 基因表达中发挥着作用。我们的结果表明去氧肾上腺素在足细胞分化过程的后期表达，并且是体内SD和FP维持和身体完整性形成的位点。去氧肾上腺素似乎在细胞存活中并不起主要作用，但对肾小球发育过程中的基因调控有很小的影响。
Nephrin, a major component of the glomerular slit diaphragm (SD), is both a structural protein as well as a signaling molecule influencing foot process (FP) formation and maintenance of podocyte integrity. Analyses of near-term embryonic kidneys showed normal cellular viability and no apoptosis in glomeruli from nephrin knockout mice. Moreover, expression and location of other SD or glomerular basement membrane components were similar in wild-type and mutant mice as was the location and levels of most podocyte-specific proteins. Transcriptional profiling showed that the lack of nephrin had minor impact on the expression of genes for FPs and SD proteins. Claudin 3, a tight-junction protein normally absent in glomeruli, was upregulated threefold in the knockout mice, suggesting a role of nephrin in claudin 3 gene expression within the glomeruli. Our results suggest that nephrin is expressed late in the process of podocyte differentiation and is a locus for the formation of SD and FP maintenance and physical integrity in vivo. Nephrin does not seem to have a primary role in cell survival but has a small impact on gene regulation during glomerular development.