Uroplakins in urothelial biology, function, and disease.
Uroplakins in urothelial biology, function, and disease.
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DOI：
10.1038/ki.2009.73
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发表时间：
2009-06
影响因子：
19.6
通讯作者：
Sun, Tung-Tien
中科院分区：
文献类型：
--
作者：
Wu, Xue-Ru;Kong, Xiang-Peng;Pellicer, Angel;Kreibich, Gert;Sun, Tung-Tien
关键词：
尿道覆盖肾盂、输尿管、膀胱和前列腺尿道的内表面。虽然形态上难以区分，在这些解剖位置的尿路上皮不同的胚胎起源和细胞分化的谱系，反映在他们不同的尿斑蛋白含量，排尿过程中的可扩展性和化学致癌物的敏感性。以前被认为是一种惰性组织，在尿液和血液之间形成一个被动的屏障，尿路上皮最近已被证明具有分泌活性，积极修改尿液成分。尿路上皮细胞表达许多离子通道、受体和配体，使它们能够接收和发送信号，并与相邻细胞及其更广泛的环境进行通信。尿路上皮细胞表面具有特异性受体，不仅允许尿路致病性E。大肠杆菌附着并侵入膀胱粘膜，但也提供了一条途径，使细菌通过输尿管上升到肾脏，引起肾盂肾炎。在小鼠中基因切除一个或多个尿斑蛋白基因会导致严重的逆行性膀胱输尿管反流、肾积水和肾衰竭，这些病症反映了某些人类先天性疾病。显然，下尿路的异常可以通过尿路上皮连接影响上尿路，反之亦然。在这篇综述中，我们强调了在尿路上皮生物学领域的最新进展，重点是尿斑蛋白，一组尿路上皮特异性和分化依赖性的完整膜蛋白。我们讨论了这些蛋白质的生物化学，结构，组装，细胞内运输及其在尿路上皮生物学，功能和病理过程中的新作用。我们还提请注意需要加大调查力度的重要领域。
Urothelium covers the inner surfaces of the renal pelvis, ureter, bladder and prostatic urethra. Although morphologically indistinguishable, the urothelia in these anatomic locations differ in their embryonic origin and lineages of cellular differentiation, as reflected in their different uroplakin content, expandability during micturition and susceptibility to chemical carcinogens. Previously thought to be an inert tissue forming a passive barrier between the urine and blood, urothelia have recently been shown to have a secretory activity that actively modifies the urine composition. Urothelial cells express a number of ion channels, receptors and ligands, enabling them to receive and send signals and communicate with adjoining cells and their broader environment. The urothelial surface bears specific receptors that not only allow uropathogenic E. coli to attach to and invade into the bladder mucosa, but also provide a route by which the bacteria ascend via the ureters to the kidney to cause pyelonephritis. Genetic ablation of one or more uroplakin genes in mice causes severe retrograde vesicoureteral reflux, hydronephrosis and renal failure, conditions that mirror certain human congenital diseases. Clearly, abnormalities of the lower urinary tract can impact on the upper tract, and vice versa, through the urothelial connection. In this review, we highlight recent advances in the field of urothelial biology by focusing on the uroplakins, a group of urothelium-specific and differentiation-dependent integral membrane proteins. We discuss these proteins’ biochemistry, structure, assembly, intracellular trafficking and their emerging roles in urothelial biology, function and pathological processes. We also call attention to important areas where greater investigative efforts are warranted.
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影响因子：
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通讯作者：
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