Ohse Takamoto, Chang Alice M, Pippin Jeffrey W, Jarad George, Hudkins Kelly L, Alpers Charles E, Miner Jeffrey H, Shankland Stuart J
Division of Nephrology, University of Washington, Seattle, WA 98195-6521, USA.
Am J Physiol Renal Physiol. 2009 Dec;297(6):F1566-74. doi: 10.1152/ajprenal.00214.2009. Epub 2009 Sep 30.
The functional role of glomerular parietal epithelial cells (PECs) remains poorly understood. To test the hypothesis that PECs form an impermeable barrier to filtered protein through the formation of tight junctions (TJ), studies were performed in normal animals and in the anti-glomerular basement membrane (GBM) model of crescentic nephritis. Electron microscopy showed well-defined TJ between PECs in normal mice, which no longer could be identified when these cells became extensively damaged or detached from their underlying Bowman's basement membrane. The TJ proteins claudin-1, zonula occludens-1, and occludin stained positive in PECs; however, staining decreased in anti-GBM disease. To show that these events were associated with increased permeability across the PEC-Bowman's basement membrane barrier, control and diseased animals were injected intravenously with either Texas red-conjugated dextran (3 kDa) or ovalbumin (45 kDa) tracers. As expected, both tracers were readily filtered across the glomerular filtration barrier and taken up by proximal tubular cells. However, when the glomerular filtration barrier was injured in anti-GBM disease, tracers were taken up by podocytes and PECs. Moreover, tracers were also detected between PECs and the underlying Bowman's basement membrane, and in many instances were detected in the extraglomerular space. We propose that together with its underlying Bowman's basement membrane, the TJ of PECs serve as a second barrier to protein. When disturbed following PEC injury, the increase in permeability of this layer to filtered protein is a mechanism underlying periglomerular inflammation characteristic of anti-GBM disease.
肾小球壁层上皮细胞（PEC）的功能作用仍未得到充分了解。为了验证PEC通过形成紧密连接（TJ）对滤过蛋白形成不可渗透屏障的假说，研究在正常动物和新月体性肾炎的抗肾小球基底膜（GBM）模型中进行。电子显微镜显示正常小鼠的PEC之间有明确的TJ，当这些细胞受到广泛损伤或与其下方的鲍曼基底膜分离时，TJ则无法再被识别。TJ蛋白claudin-1、闭合蛋白1和封闭蛋白在PEC中呈阳性染色；然而，在抗GBM疾病中染色减少。为了表明这些事件与PEC - 鲍曼基底膜屏障通透性增加有关，对对照动物和患病动物静脉注射Texas红偶联葡聚糖（3 kDa）或卵清蛋白（45 kDa）示踪剂。正如预期的那样，两种示踪剂都很容易通过肾小球滤过屏障，并被近端肾小管细胞摄取。然而，当抗GBM疾病导致肾小球滤过屏障受损时，示踪剂被足细胞和PEC摄取。此外，在PEC与下方的鲍曼基底膜之间也检测到示踪剂，并且在许多情况下在肾小球外间隙中也检测到。我们提出，PEC的TJ与其下方的鲍曼基底膜一起，作为蛋白质的第二道屏障。当PEC损伤后TJ受到干扰时，该层对滤过蛋白通透性的增加是抗GBM疾病特征性的肾小球周围炎症的潜在机制。
