Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis

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 Up...

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Bibliographic Details
Published in:	Kidney international Vol. 89; no. 3; p. 612
Main Authors:	Carpenter, Ashley R, Becknell, M Brian, Ching, Christina B, Cuaresma, Edward J, Chen, Xi, Hains, David S, McHugh, Kirk M
Format:	Journal Article
Language:	English
Published:	United States 01-03-2016
Subjects:	Animals Cell Differentiation Cell Proliferation Gene Expression Regulation, Developmental Genotype Homeostasis Hydronephrosis - genetics Hydronephrosis - metabolism Kidney - abnormalities Kidney - metabolism Kidney - ultrastructure Mice, Knockout Phenotype Signal Transduction Tetraspanins - deficiency Tetraspanins - genetics Tetraspanins - metabolism Urinary Bladder - abnormalities Urinary Bladder - metabolism Urinary Bladder - ultrastructure Urogenital Abnormalities - genetics Urogenital Abnormalities - metabolism Urothelium - abnormalities Urothelium - metabolism Urothelium - ultrastructure Vesico-Ureteral Reflux - genetics Vesico-Ureteral Reflux - metabolism kidney CAKUT development uroplakins urothelium bladder
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Summary:	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. Upk1b(RFP/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. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/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.
ISSN:	1523-1755
DOI:	10.1016/j.kint.2015.11.017