Cloning of rat homologue of podocin: Expression in proteinuric states and in developing glomeruli
Cloning of rat homologue of podocin: Expression in proteinuric states and in developing glomeruli
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DOI：
10.1097/01.asn.0000037401.02391.76
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发表时间：
2003-01-01
影响因子：
13.6
通讯作者：
Shimizu, F
中科院分区：
文献类型：
--
作者：
Kawachi, H;Koike, H;Shimizu, F
Podocin被鉴定为常染色体隐性遗传类固醇耐药肾病综合征患者基因突变的产物。尽管据报道podocin位于狭缝光阑区域，但podocin用于维持狭缝光阑的屏障功能的确切作用尚未清楚阐明。克隆了podocin的大鼠同源物，并研究了podocin的表达，然后将其与nephrin和ZO-1在大鼠实验性蛋白尿模型和发育中的肾小球中的表达进行比较。大鼠和人podocin的氨基酸序列高度同源（84.3%同一性）。podocin的结构域结构在大鼠和人类之间也是高度保守的。肾小球和神经组织中检测到podocin mRNA的表达。podocin在正常成年大鼠肾小球中的定位与nephrin非常接近。Podocin染色仅限于发育早期足细胞的基底侧，而nephrin染色在足细胞的基底外侧表面上检测到。在抗nephrin抗体（ANA）诱导的肾病和嘌呤霉素氨基糖苷（PAN）肾病中观察到podocin的重新分布。podocin与nephrin在ANA肾病中的重新分布，而在PAN肾病中则没有。在PAN肾病蛋白尿状态下，在新形成的紧密连接部位观察到Podocin。据推测，podocin是维持肾小球毛细血管壁屏障功能的狭缝隔膜的关键组分之一。kawachi@med.niigata-u.ac.jl.
Podocin is identified as a product of the gene mutated in a patient with autosomal recessive steroid-resistant nephrotic syndrome. Although podocin is reported to be located at the slit diaphragm area, the precise role of podocin for maintaining the barrier function of the slit diaphragm has not been clearly elucidated. A rat homologue of podocin was cloned, and the expression of podocin was investigated and then compared with the nephrin and the ZO-1 expressions in rat experimental proteinuric models and in developing glomeruli. Amino acid sequences of rat and human podocin are highly homologous (84.3% identity). The domain structure of podocin is also highly conserved between rat and human. The mRNA expression for podocin was detected in glomeruli and the nerve tissues. The localization of podocin has close proximity to that of nephrin in normal adult rat glomeruli. Podocin staining was restricted to the basal side of the podocyte of the early developing stage, whereas nephrin staining was detected on the basolateral surface of podocyte. The redistribution of podocin was observed in the anti-nephrin antibody (ANA)-induced nephropathy and puromycin aminonucleoside (PAN) nephropathy. The redistribution of podocin paralleled with nephrin in ANA nephropathy but not in PAN nephropathy. Podocin is observed at the site of tight junction newly formed in proteinuric state in PAN nephropathy. It is postulated that podocin is one of the critical components of a slit diaphragm for maintaining the barrier function of the glomerular capillary wall. kawachi@med.niigata-u.ac.jl.