Bladder permeability barrier: recovery from selective injury of surface epithelial cells
Bladder permeability barrier: recovery from selective injury of surface epithelial cells
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DOI：
10.1152/ajprenal.00307.2001
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Zeidel, ML
中科院分区：
文献类型：
--
作者：
Lavelle, J;Meyers, S;Zeidel, ML
哺乳动物膀胱在尿液和血液之间维持高电化学梯度，允许肾脏通过尿液排泄改变身体化学成分。为了执行此功能，尿路上皮保持紧密的渗透性屏障。当该屏障受损时，尿液成分会渗漏到下面的膀胱层中，从而出现膀胱炎的症状。在这些研究中，我们使用硫酸鱼精蛋白 (PS) 开发了选择性尿路上皮损伤模型，并定义了该上皮从损伤中恢复的过程。暴露于PS（10 mg/ml）而非媒介物会导致跨上皮阻力迅速下降以及水和尿素渗透性的显着增加。通过扫描和透射电子显微镜观察到，这些变化伴随着伞状细胞片的坏死和脱落。 PS 暴露后 72 小时内，屏障功能恢复，跨上皮阻力以及水和尿素渗透性恢复到正常值。伞细胞丢失后，下面的中间细胞经历快速成熟，尿斑蛋白表达增加和边界明确的紧密连接逐渐形成就证明了这一点。在 PS 暴露后第 5 天，屏障功能恢复，表面细胞表现出正常外观的紧密连接以及尿斑蛋白和闭合小带 1 的正常标记。然而，细胞仍然小于伞细胞，直到暴露后第 10 天，此时恢复正常大小。这些研究首次开发了选择性尿路上皮损伤的受控模型，并证明了屏障功能恢复和潜在中间细胞发育成成熟伞细胞的特征过程。该模型将有助于定义调节尿路上皮损伤修复的机制。
The mammalian bladder maintains high electrochemical gradients between urine and blood, permitting the kidney to modify body chemistries through urinary excretion. To perform this function, the urothelium maintains a tight permeability barrier. When this barrier is damaged, leakage of urine components into the underlying bladder layers results, with symptoms of cystitis. In these studies, we develop a model of selective urothelial injury using protamine sulfate (PS) and define the process by which this epithelium recovers from damage. Exposure to PS (10 mg/ml), but not vehicle, caused a rapid fall in transepithelial resistance as well as striking increases in water and urea permeabilities. These changes were accompanied by necrosis and sloughing of sheets of umbrella cells, as seen by scanning and transmission electron microscopy. Over the 72 h after PS exposure, barrier function recovered, with transepithelial resistance and water and urea permeabilities returning to normal values. After loss of umbrella cells, the underlying intermediate cells underwent rapid maturation, as evidenced by increased expression of uroplakins and gradual formation of well-defined tight junctions. At day 5 after PS exposure, barrier function was restored and the surface cells exhibited normal-appearing tight junctions and normal labeling for uroplakins and zonula occludens 1. However, the cells remained smaller than umbrella cells until day 10 after exposure, when normal size was restored. These studies develop for the first time a controlled model of selective urothelial damage and demonstrate a characteristic process by which barrier function is restored and underlying intermediate cells develop into mature umbrella cells. This model will be useful in defining the mechanisms that regulate repair of urothelial damage.