Ablation of Uroplakin III Gene Results in Small Urothelial Plaques, Urothelial Leakage, and Vesicoureteral Reflux

Journal of Cell Biology - Tập 151 Số 5 - Trang 961-972 - 2000
Ping Hu1,2, Fang‐Ming Deng1, Feng‐Xia Liang1, Chuanmin Hu1, Anna B. Auerbach3, Ellen Shapiro4, Xue‐Ru Wu4,5,6, Bechara Kachar7, Tung‐Tien Sun1,2,4
1aEpithelial Biology Unit, The Ronald O. Perelman Department of Dermatology, New York, New York 10016
2bDepartment of Pharmacology, New York, New York 10016
3cSkirball Institute of Biomolecular Medicine, New York, New York 10016
4dDepartment of Urology, New York, New York 10016
5eDepartment of Microbiology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016
6fVeterans Administration Medical Center, New York, New York 10010
7gSection on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892

Tóm tắt

Urothelium synthesizes a group of integral membrane proteins called uroplakins, which form two-dimensional crystals (urothelial plaques) covering >90% of the apical urothelial surface. We show that the ablation of the mouse uroplakin III (UPIII) gene leads to overexpression, defective glycosylation, and abnormal targeting of uroplakin Ib, the presumed partner of UPIII. The UPIII-depleted urothelium features small plaques, becomes leaky, and has enlarged ureteral orifices resulting in the back flow of urine, hydronephrosis, and altered renal function indicators. Thus, UPIII is an integral subunit of the urothelial plaque and contributes to the permeability barrier function of the urothelium, and UPIII deficiency can lead to global anomalies in the urinary tract. The ablation of a single urothelial-specific gene can therefore cause primary vesicoureteral reflux (VUR), a hereditary disease affecting ∼1% of pregnancies and representing a leading cause of renal failure in infants. The fact that VUR caused by UPIII deletion seems distinct from that caused by the deletion of angiotensin receptor II gene suggests the existence of VUR subtypes. Mutations in multiple gene, including some that are urothelial specific, may therefore cause different subtypes of primary reflux. Studies of VUR in animal models caused by well-defined genetic defects should lead to improved molecular classification, prenatal diagnosis, and therapy of this important hereditary problem.

Từ khóa


Tài liệu tham khảo

Ambrose, 1969, Reflux pyelonephritis in adults secondary to congenital lesions of the ureteral orifice, J. Urol., 102, 302, 10.1016/S0022-5347(17)62133-5

Atala, 1998, Vesicoureteral reflux and megaureter, Campbell's Urology, 1859

Atwell, 1985, Familial pelviureteric junction hydronephrosis and its association with a duplex pelvicaliceal system and vesicoureteric reflux. A family study, Br. J. Urol, 57, 365, 10.1111/j.1464-410X.1985.tb06289.x

Bailey, 1984, Familial and genetic data in reflux nephropathy, Reflux Nephropathy Update, 40

Becker, 1995, Congenital nephropathies and uropathies, Pediatr. Clin. N. Am, 42, 1319, 10.1016/S0031-3955(16)40087-8

Belman, 1997, Vesicoureteral reflux, Pediatr. Clin. N. Am, 44, 1171, 10.1016/S0031-3955(05)70552-6

Brisson, 1983, Three-dimensional structure of luminal plasma membrane protein from urinary bladder, J. Mol. Biol., 166, 21, 10.1016/S0022-2836(83)80048-5

Chang, 1994, Permeability properties of the mammalian bladder apical membrane, Am. J. Physiol, 267, C1483, 10.1152/ajpcell.1994.267.5.C1483

Chapman, 1985, Vesicoureteric refluxsegregation analysis, Am. J. Med. Genet, 20, 577, 10.1002/ajmg.1320200403

de Vargas, 1978, A family study of vesicoureteric reflux, J. Med. Genet, 15, 85, 10.1136/jmg.15.2.85

Devriendt, 1998, Vesico-ureteral refluxa genetic condition?, Eur. J. Pediatr, 157, 265, 10.1007/s004310050808

Dillon, 1998, Reflux nephropathy, J. Am. Soc. Nephrol, 9, 2377, 10.1681/ASN.V9122377

Eccles, 1996, Unravelling the genetics of vesicoureteric refluxa common familial disorder, Hum. Mol. Genet, 5, 1425, 10.1093/hmg/5.Supplement_1.1425

Feather, 2000, Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1, Am. J. Hum. Genet, 66, 1420, 10.1086/302864

Finch, 1997, Chromosomal localization of the human urothelial “tetraspan” gene, UPK1B, to 3q13.3-q21 and detection of a TaqI polymorphism, Genomics, 40, 501, 10.1006/geno.1996.4589

Fukui, 1983, In vivo staining test with methylene blue for bladder cancer, J. Urol., 130, 252, 10.1016/S0022-5347(17)51088-5

Garin, 1998, Primary vesicoureteral refluxreview of current concepts, Pediatr. Nephrol, 12, 249, 10.1007/s004670050448

Hicks, 1965, The fine structure of the transitional epithelium of rat ureter, J. Cell Biol., 26, 25, 10.1083/jcb.26.1.25

Hicks, 1975, The mammalian urinary bladderan accommodating organ, Biol. Rev. Camb. Philos. Soc., 50, 215, 10.1111/j.1469-185X.1975.tb01057.x

Hicks, 1969, Hexagonal lattice of subunits in the thick luminal membrane of the rat urinary bladder, Nature, 224, 1304, 10.1038/2241304a0

Hiraoka, 1999, Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography, Kidney Int, 55, 1486, 10.1046/j.1523-1755.1999.00380.x

Horowitz, 1999, Vesicoureteral reflux in infants with prenatal hydronephrosis confirmed at birthracial differences, J. Urol, 161, 248, 10.1016/S0022-5347(01)62121-9

Kachar, 1999, Three-dimensional analysis of the 16 nm urothelial plaque particleluminal surface exposure, preferential head-to-head interaction, and hinge formation, J. Mol. Biol, 285, 595, 10.1006/jmbi.1998.2304

Kincaid-Smith, 1984, Relux nephropathy in the adult, Contrib. Nephrol, 39, 94, 10.1159/000409238

King, 1992, Vesicoureteral reflux, megaureter, and ureteral reimplantation, Campbell's Urology, 1689

Koss, 1969, The asymmetric unit membranes of the epithelium of the urinary bladder of the rat. An electron microscopic study of a mechanism of epithelial maturation and function, Lab. Invest, 21, 154

Lewis, 1982, Incorporation of cytoplasmic vesicles into apical membrane of mammalian urinary bladder epithelium, Nature, 297, 685, 10.1038/297685a0

Liang, 1999, Urothelial hinge as a highly specialized membranedetergent-insolubility, urohingin association, and in vitro formation, Differentiation, 65, 59, 10.1046/j.1432-0436.1999.6510059.x

Lin, 1994, Precursor sequence, processing, and urothelium-specific expression of a major 15-kDa protein subunit of asymmetric unit membrane, J. Biol. Chem, 269, 1775, 10.1016/S0021-9258(17)42095-3

Lyon, 1969, The ureteral orificeits configuration and competency, J. Urol., 102, 504, 10.1016/S0022-5347(17)62184-0

Minsky, 1978, Morphometric analysis of the translocation of lumenal membrane between cytoplasm and cell surface of transitional epithelial cells during the expansion-contraction cycles of mammalian urinary bladder, J. Cell Biol, 77, 685, 10.1083/jcb.77.3.685

Negrete, 1996, Permeability properties of the intact mammalian bladder epithelium, Am. J. Physiol, 271, F886

Nishimura, 1999, Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men, Mol. Cell, 3, 1, 10.1016/S1097-2765(00)80169-0

Noe, 1992, The transmission of vesicoureteral reflux from parent to child, J. Urol, 148, 1869, 10.1016/S0022-5347(17)37053-2

1999

Peeden, 1992, Is it practical to screen for familial vesicoureteral reflux within a private pediatric practice?, Pediatrics, 89, 758, 10.1542/peds.89.4.758

Pope, 1999, How they begin and how they endclassic and new theories for the development and deterioration of congenital anomalies of the kidney and urinary tract, CAKUT, J. Am. Soc. Nephrol, 10, 2018, 10.1681/ASN.V1092018

Porter, 1963, The Fine Structure of Cells and Tissues

Ramirez-Solis, 1993, Gene targeting in embryonic stem cells, Methods Enzymol., 225, 855, 10.1016/0076-6879(93)25054-6

Riedel, 2000, Brenner tumors but not transitional cell carcinomas of the ovary show urothelial differentiationimmunohistochemical staining of urothelial markers, including cytokeratins and uroplakin III, Virchows Archiv, In press

Roberts, 1992, Vesicoureteral reflux and pyelonephritis in the monkeya review, J. Urol, 148, 1721, 10.1016/S0022-5347(17)37013-1

Sant, 1999, Interstitial cystitis, Curr. Opin. Urol, 9, 297, 10.1097/00042307-199907000-00004

Shapiro, 1984, The inheritance of the exstrophy-epispadias complex, J. Urol, 132, 308, 10.1016/S0022-5347(17)49605-4

Smellie, 1979, Reflux nephropathy in childhood, Feflux Nephropathy, 14

Staehelin, 1972, Lumenal plasma membrane of the urinary bladder. I. Three-dimensional reconstruction from freeze-etch images, J. Cell Biol, 53, 73, 10.1083/jcb.53.1.73

Sun, 1984, Classification, expression, and possible mechanisms of evolution of mammalian epithelial keratinsa unifying model, The Cancer CellThe Transformed Phenotype. Vol. 1, 169

Sun, 1999, Uroplakins as markers of urothelial differentiation, Adv. Exp. Med. Biol, 462, 7, 10.1007/978-1-4615-4737-2_1

Surya, 1990, Assessing the differentiation state of cultured bovine urothelial cellselevated synthesis of stratification-related K5 and K6 keratins and persistent expression of uroplakin I, J. Cell Sci, 97, 419, 10.1242/jcs.97.3.419

Tseng, 1982, Correlation of specific keratins with different types of epithelial differentiationmonoclonal antibody studies, Cell, 30, 361, 10.1016/0092-8674(82)90234-3

Vergara, 1969, A hexagonal arrangement of subunits in membrane of mouse urinary bladder, J. Mol. Biol., 46, 593, 10.1016/0022-2836(69)90200-9

Walz, 1995, Towards the molecular architecture of the asymmetric unit membrane of the mammalian urinary bladder epitheliuma closed “twisted ribbon” structure, J. Mol. Biol, 248, 887, 10.1006/jmbi.1995.0269

Wu, 1994, Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins, J. Biol. Chem, 269, 13716, 10.1016/S0021-9258(17)36889-8

Wu, 1990, Large scale purification and immunolocalization of bovine uroplakins I, II, and III. Mol markers of urothelial differentiation, J. Biol. Chem, 265, 19170, 10.1016/S0021-9258(17)30640-3

Wu, 1995, Selective interactions of UPIa and UPIb, two members of the transmembrane 4 superfamily, with distinct single transmembrane-domained proteins in differentiated urothelial cells, J. Biol. Chem, 270, 29752, 10.1074/jbc.270.50.29752

Wu, 1993, Molecular cloning of a 47 kDa tissue-specific and differentiation-dependent urothelial cell surface glycoprotein, J. Cell Sci, 106, 31, 10.1242/jcs.106.1.31

Yu, 1994, Uroplakins Ia and Ib, two major differentiation products of bladder epithelium, belong to a family of four transmembrane domain (4TM) proteins, J. Cell Biol, 125, 171, 10.1083/jcb.125.1.171

Yu, 1992, Identification of an 85-100 kDa glycoprotein as a cell surface marker for an advanced stage of urothelial differentiationassociation with the inter-plaque (‘hinge’) area, Epithelial Cell Biol, 1, 4

Yu, 1990, Uroplakin Ia 27-kD protein associated with the asymmetric unit membrane of mammalian urothelium, J. Cell Biol, 111, 1207, 10.1083/jcb.111.3.1207

Thông tin
Thông tin xuất bản

Journal of Cell Biology

Tập 151 Số 5

961-972

Thông tin tác giả