Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.
Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.
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DOI：
10.1016/j.kint.2015.11.017
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发表时间：
2016-03
影响因子：
19.6
通讯作者：
McHugh KM
中科院分区：
文献类型：
--
作者：
Carpenter AR;Becknell MB;Ching CB;Cuaresma EJ;Chen X;Hains DS;McHugh KM
正确的发育和维护尿道对它的功能至关重要。尿斑蛋白在发育和成熟的尿路上皮中表达，在那里它们建立与渗透性屏障相关的斑块。它们在发育和疾病中的确切功能作用尚不清楚。在这里，我们在体内破坏了Upk 1b，其损失导致膀胱和肾脏中的尿路上皮斑块破坏。Upk 1bRFP/RFP膀胱尿路上皮出现发育不良，祖细胞标志物Krt 14和Krt 5扩增，Shh表达增加，终末分化标志物Krt 20和尿斑蛋白丢失。Upk 1bRFP/RFP肾尿路上皮分层，细胞组成改变。Upk 1bRFP/RFP小鼠出现年龄依赖性进行性肾积水。有趣的是，16%的Upk 1bRFP/RFP小鼠具有单侧双肾。我们的研究扩展了uroplakins的作用，从机制上将斑块形成与尿路发育和功能联系起来，并提供了先天性肾脏和尿路异常沿着各种尿路疾病中观察到的功能缺陷之间的诱人联系。因此，肾脏和膀胱尿路上皮是区域性不同的，并保持高度的可塑性，能够通过组织特异性祖细胞群体的扩展。此外，Upk 1b在早期肾脏发育中起着以前未知的作用，代表了肾脏和泌尿道先天性异常的新遗传靶点。
Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1bRFP/RFP bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1bRFP/RFP renal urothelium became stratified with altered cellular composition. Upk1bRFP/RFP mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1bRFP/RFP mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract.