Podocin is translocated to cytoplasm in puromycin aminonucleoside nephrosis rats and in poor-prognosis patients with IgA nephropathy.
Podocin is translocated to cytoplasm in puromycin aminonucleoside nephrosis rats and in poor-prognosis patients with IgA nephropathy.
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DOI：
10.1007/s00441-014-2100-9
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发表时间：
2015-05
影响因子：
3.6
通讯作者：
Tomino Y
中科院分区：
文献类型：
--
作者：
Fukuda H;Hidaka T;Takagi-Akiba M;Ichimura K;Oliva Trejo JA;Sasaki Y;Wang J;Sakai T;Asanuma K;Tomino Y
足细胞通过称为狭缝膜的高度专门化结构作为尿蛋白丢失的最终屏障，并维持足突和肾小球基底膜。足细胞损伤导致肾小球进行性损害，加速肾小球硬化，但其确切机制尚不清楚。我们专注于染色间隙（podocin间隙）定义为podocin和synaptopodin之间的染色差异，通常位于足突。在嘌呤霉素氨基糖苷肾病大鼠中，podocin间隙显著增加（p < 0.05），podocin在第7天和第14天易位到细胞质中，但在第28天没有。令人惊讶的是，在预后不良的伊加肾病患者的人肾活检标本中，差距也显著增加（p < 0.05）。这表明podocin缺口可能是一个有用的标志物，用于分类伊加肾病的预后和指示podocin易位到细胞质。接下来，我们发现了更多的证据，足细胞中的podocin贩运，其中podocin与Rab5在嘌呤霉素氨基糖苷肾病大鼠在第14天合并。免疫电镜观察，在嘌呤霉素肾病大鼠第7天和第14天，足突区podocin阳性区域明显移位至胞浆（p< 0.05）。有趣的是，podocin在预后不良的人伊加肾病中也易位到细胞质中。在本文中，我们证明了通过内吞作用引起的podocin移位可能是关键足细胞损伤的关键交通事件，并且podocin缺口可以指示伊加肾病的预后。
Podocytes serve as the final barrier to urinary protein loss through a highly specialized structure called a slit membrane and maintain foot process and glomerular basement membranes. Podocyte injury results in progressive glomerular damage and accelerates sclerotic changes, although the exact mechanism of podocyte injury is still obscure. We focus on the staining gap (podocin gap) defined as the staining difference between podocin and synaptopodin, which are normally located in the foot process. In puromycin aminonucleoside nephrosis rats, the podocin gap is significantly increased (p < 0.05) and podocin is translocated to the cytoplasm on days 7 and 14 but not on day 28. Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients. This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm. Next, we find more evidence of podocin trafficking in podocytes where podocin merges with Rab5 in puromycin aminonucleoside nephrosis rats at day 14. In immunoelectron microscopy, the podocin positive area was significantly translocated from the foot process areas to the cytoplasm (p< 0.05) on days 7 and 14 in puromycin aminonucleoside nephrosis rats. Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy. In this paper, we demonstrate that the translocation of podocin by endocytosis could be a key traffic event of critical podocyte injury and that the podocin gap could indicate the prognosis of IgA nephropathy.