Uroplakin III
Uroplakin Ib
Uroplakin II
Uroplakin Ia
Brenner Tumor
Tetraspanins
Immunohistochemical analysis of uroplakins, urothelial specific proteins, in ovarian Brenner tumors, normal tissues, and benign and neoplastic lesions of the female genital tract. (1/46)
Uroplakins are the characteristic integral membrane proteins in terminally differentiated, superficial urothelial asymmetric unit membrane. Brenner tumors of the ovary and Walthard cell nests of Fallopian tubes have been considered to represent urothelial differentiation in the female genital tract, but no definitive differentiation marker has been demonstrated supporting such a conclusion. An immunohistochemical analysis was performed to assess the expression of uroplakins in these lesions as well as in various benign and neoplastic lesions and normal tissues of the female genital tract. Focal expression of uroplakins was observed on the luminal surface of ovarian Brenner tumor cells forming microcysts in all 5 cases examined. In contrast, uroplakins were slightly expressed in only 1 of 12 cases of Walthard cell nests, even in the presence of microcyst formation. Uroplakins were not expressed in other benign or malignant lesions or normal tissues of the female genital tract. These results support the hypothesis that the Brenner tumor and possibly Walthard cell nests represent urothelial (transitional cell) differentiation. (+info)Comparison of uroplakin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats and mice. (2/46)
The expression of uroplakins, the tissue-specific and differentiation-dependent membrane proteins of the urothelium, was analyzed immunohistochemically in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats and mice during bladder carcinogenesis. Male Fischer 344 rats were treated with 0.05% BBN in the drinking water for 10 wk and were euthanatized at week 20 of the experiment. BBN was administered to male B6D2F, mice; it was either provided at a rate of 0.05% in the drinking water (for 26 wk) or 5 mg BBN was administered by intragastric gavage twice weekly for 10 wk, followed by 20 wk without treatment. In rats, BBN-induced, noninvasive, low-grade, papillary, transitional cell carcinoma (TCC) showed decreased uroplakin-staining of cells lining the lumen but showed increased expression in some nonluminal cells. In mice, nonpapillary, high-grade dysplasia, carcinoma in situ, and invasive carcinoma were induced. There was a marked decrease in the number of uroplakin-positive cells lining the lumen and in nonluminal cells. This occurred in normal-appearing urothelium in BBN-treated mice and in dysplasic urothelium, in carcinoma in situ, and in invasive TCC. The percentage of uroplakin-positive nonluminal cells was higher in control mice than in rats, but it was lower in the mouse than in the rat after BBN treatment. Uroplakin expression was disorderly and focal in BBN-treated urothelium in both species. These results indicate that BBN treatment changed the expression of uroplakins during bladder carcinogenesis, with differences in rats and mice being related to degree of tumor differentiation. (+info)Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas. (3/46)
Uroplakins are specific differentiation products of terminally differentiated superficial urothelial cells. We tested the value of a new commercially available monoclonal antibody against uroplakin III (clone AU 1) as a paraffin-reactive immunohistochemical marker for primary and metastatic urothelial carcinomas. The study cases included 67 urothelial carcinomas of the urinary tract (35 primary tumors, 32 metastases) and 318 nonurothelial carcinomas, as well as 5 benign Brenner tumors and 2 transitional cell carcinomas of the ovaries. Uroplakin III was detected in 21 (60%) of the primary urothelial carcinomas and 17 (53%) of the metastases, resulting in an overall sensitivity of 0.57. The studied Brenner tumors also were immunoreactive for uroplakin III. All other studied carcinomas were consistently uroplakin III-negative (specificity 1.00). We found the new monoclonal antibody AU 1 against uroplakin III to be a highly specific paraffin-reactive immunohistochemical marker for urothelial tumors with a moderate sensitivity for the identification of primary and metastatic urothelial carcinomas. (+info)Terminal glycosylation of bovine uroplakin III, one of the major integral-membrane glycoproteins of mammalian bladder. (4/46)
Uroplakin III (UPIII) is one of the major transmembrane glycoproteins exposed at the luminal face of mammalian bladder. We investigated the terminal glycosylation of bovine UPIII in order to ascertain whether it contains the alpha 2,3-sialylated sequence thus potentially serving as a receptor for uropathogenic Escherichia coli expressing type S adhesins. We report the occurrence of sialic acid in alpha 2,3- and alpha 2,6-linkage to galactose in bovine UPIII glycans as evidenced by the sensitivity of UPIII to both Vibrio cholera and Newcastle disease virus neuraminidase and by the colocalization of UPIII antigen and material detected by lectins of Sambucus nigra and Maackia amurensis on the luminal face of the bladder. We also present evidence that UPIII glycans are capped by Gal-alpha 1,3-Gal epitope. Consistently, alpha 2,3- and alpha 2, 6-sialyltransferase, as well as alpha 1,3-galactosyltransferase were found to be present in the cells detached from the luminal side of bovine bladder, which are responsible for the UPIII biosynthesis. The putative role of UPIII sialylated glycans in enhancing the uropathogenicity of E. coli expressing type S adhesins is discussed. (+info)Human uroplakin Ib in ocular surface epithelium. (5/46)
PURPOSE: To investigate the expression and localization of the human gene encoding uroplakin Ib in ocular surface epithelium. METHODS: The full-length cDNA of human uroplakin Ib was isolated from a cDNA library of human corneal epithelium, and the expression of uroplakin Ib in various tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR). In cornea and conjunctiva, the expressions of uroplakin Ia, II, and III were also examined by RT-PCR. Finally, the localization of uroplakin Ib in the ocular surface was analyzed by immunofluorescence confocal microscopy, by using an antiserum against a synthetic peptide. RESULTS: Two mRNA isoforms, arising through two polyadenylation sites, were isolated. RT-PCR detected uroplakin Ib in cornea, conjunctiva, bladder, placenta, and kidney. Among other uroplakins, uroplakin II was also faintly detected in cornea and conjunctiva. Immunofluorescence confocal microscopy documented uroplakin Ib protein in the cell membranes of superficial and wing cells in the corneal epithelium. It was not found, however, in the most apical corneal epithelial cells. In limbus and conjunctiva, uroplakin Ib was also localized in the cell membranes of all epithelial layers, apart from the most apical cells. CONCLUSIONS: Uroplakin Ib is highly expressed in ocular surface epithelia. As in bladder epithelium, uroplakin Ib may protect the ocular surface from bacterial infection. (+info)Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux. (6/46)
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 approximately 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. (+info)Stretch-regulated exocytosis/endocytosis in bladder umbrella cells. (7/46)
The epithelium of the urinary bladder must maintain a highly impermeable barrier despite large variations in urine volume during bladder filling and voiding. To study how the epithelium accommodates these volume changes, we mounted bladder tissue in modified Ussing chambers and subjected the tissue to mechanical stretch. Stretching the tissue for 5 h resulted in a 50% increase in lumenal surface area (from approximately 2900 to 4300 microm(2)), exocytosis of a population of discoidal vesicles located in the apical cytoplasm of the superficial umbrella cells, and release of secretory proteins. Surprisingly, stretch also induced endocytosis of apical membrane and 100% of biotin-labeled membrane was internalized within 5 min after stretch. The endocytosed membrane was delivered to lysosomes and degraded by a leupeptin-sensitive pathway. Last, we show that the exocytic events were mediated, in part, by a cyclic adenosine monophosphate, protein kinase A-dependent process. Our results indicate that stretch modulates mucosal surface area by coordinating both exocytosis and endocytosis at the apical membrane of umbrella cells and provide insight into the mechanism of how mechanical forces regulate membrane traffic in non-excitable cells. (+info)Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. (8/46)
Although water, small nonelectrolytes, and gases are freely permeable through most biological membranes, apical membranes of certain barrier epithelia exhibit extremely low permeabilities to these substances. The role of integral membrane proteins in this barrier function has been unclear. To study this problem, we have ablated the mouse gene encoding uroplakin III (UPIII), one of the major protein subunits in urothelial apical membranes, and measured the permeabilities of these membranes. Ablation of the UPIII gene greatly diminishes the amounts of uroplakins on the apical urothelial membrane (Hu P, Deng FM, Liang FX, Hu CM, Auerbach AB, Shapiro E, Wu XR, Kachar B, and Sun TT. J Cell Biol 151: 961-972, 2000). Our results indicate that normal mouse urothelium exhibits high transepithelial resistance and low urea and water permeabilities. The UPIII-deficient urothelium exhibits a normal transepithelial resistance (normal 2,024 +/- 122, knockout 2,322 +/- 114 Omega. cm(2); P > 0.5). However, the UPIII-deficient apical membrane has a significantly elevated water permeability (normal 0.91 +/- 0.06, knockout 1.83 +/- 0.14 cm/s x 10(-5); P < 0.05). The urea permeability of the UPIII-deficient membrane also increased, although to a lesser extent (normal 2.22 +/- 0.24, knockout 2.93 +/- 0.31 cm/s x 10(-6); P = 0.12). These results indicate that reduced targeting of uroplakins to the apical membrane does not significantly alter the tight junctional barrier but does double the water permeability. We provide the first demonstration that integral membrane proteins contribute to the apical membrane permeability barrier function of urothelium. (+info)Uroplakin III is a protein that is a component of urothelial plaques, which are specialized structures found on the surface of urothelial cells in the urinary bladder. Urothelial plaques play an important role in maintaining the barrier function and permeability properties of the urothelium.
Uroplakin III is a member of the uroplakin family of proteins, which includes UPIa, UPII, UPIII, and UPIIIA. These proteins are synthesized in the endoplasmic reticulum and transported to the Golgi apparatus, where they form heterodimers that are then transported to the plasma membrane. At the plasma membrane, the heterodimers assemble into larger complexes called urothelial plaques.
Uroplakin III is a transmembrane protein with a molecular weight of approximately 27 kDa. It has been shown to play a role in the formation and stability of urothelial plaques, as well as in the regulation of ion transport across the urothelium. Mutations in the gene encoding Uroplakin III have been associated with certain bladder diseases, including interstitial cystitis/bladder pain syndrome and bladder cancer.
Uroplakin Ib is not a recognized medical term or concept in and of itself. However, Uroplakins are a group of proteins found on the surface of urothelial cells, which make up the lining of the urinary tract. These proteins play an important role in maintaining the barrier function and integrity of the urothelium.
Uroplakin Ib is one of four major uroplakins (Ia, Ib, II, and III) that form complexes called uroplakins plaques on the apical surface of superficial urothelial cells. These plaques are thought to provide a protective barrier against urinary constituents, as well as contribute to the low permeability of the urothelium.
Therefore, while "Uroplakin Ib" may not have its own medical definition, it is an important component of the larger structure and function of uroplakins in the urinary tract.
Uroplakin II is a type of protein that is a component of the urothelium, which is the tissue that lines the urinary tract. Specifically, uroplakins are part of the asymmetric unit membrane (AUM) of the urothelial plaques, which are specialized structures on the apical surface of the urothelium. These plaques help to provide a barrier function and protect the underlying tissues from various harmful substances in the urine. Uroplakin II is a transmembrane protein that forms heterodimers with other uroplakins, such as uroplakin Ib, to create the building blocks of the urothelial plaques.
Uroplakin Ia is not a medical term itself, but it is a component of uroplakins which are a group of proteins found in the urothelium, the tissue that lines the urinary tract. Uroplakins are involved in the formation of the asymmetric unit membrane (AUM) of the urothelial plaques, which are specialized structures on the apical surface of the superficial urothelial cells. These plaques provide a barrier function and protect the underlying tissues from various harmful substances in urine.
Uroplakin Ia is one of the four major uroplakins (UPIa, UPIb, UPII, and UPIII) that form heterodimers and then assemble into larger complexes to form the urothelial plaques. Specifically, Uroplakin Ia combines with Uroplakin Ib to form a heterodimer, which then associates with UPII and UPIII heterodimers to form a tetraspanin complex. These complexes are then incorporated into the AUM of the urothelial plaques.
Abnormalities in uroplakins have been associated with various urological disorders, including bladder cancer, interstitial cystitis, and chronic pelvic pain syndrome.
A Brenner tumor is a rare type of benign (non-cancerous) ovarian tumor that originates from the tissue that lines the ovary (the epithelium). These tumors are typically small, slow-growing, and asymptomatic, although in some cases they may cause abdominal discomfort or bloating.
Brenner tumors are composed of transitional cells, which are similar to the cells found in the urinary bladder. They are usually solid and contain areas of calcification (calcium deposits). While most Brenner tumors are benign, a small percentage may become malignant (cancerous) and spread to other parts of the body.
The exact cause of Brenner tumors is not known, but they are more common in older women and are often found incidentally during routine pelvic exams or imaging studies. Treatment typically involves surgical removal of the tumor, and the prognosis is generally excellent, especially for benign tumors.
Urothelium is the specialized type of epithelial tissue that lines the urinary tract, including the renal pelvis, ureters, bladder, and urethra. It is a type of transitional epithelium that can change its shape and size depending on the degree of distension or stretching of the organs it lines.
The main function of urothelium is to provide a barrier against urine, which contains various waste products and potential irritants, while also allowing the exchange of ions and water. The urothelial cells are joined together by tight junctions that prevent the passage of substances through the paracellular space, and they also have the ability to transport ions and water through their cell membranes.
In addition to its barrier function, urothelium is also involved in sensory and immune functions. It contains specialized nerve endings that can detect mechanical and chemical stimuli, such as stretch or irritation, and it expresses various antimicrobial peptides and other defense mechanisms that help protect the urinary tract from infection.
Overall, urothelium plays a critical role in maintaining the health and function of the urinary tract, and its dysfunction has been implicated in various urinary tract disorders, such as interstitial cystitis/bladder pain syndrome and bladder cancer.
Tetraspanins are a family of membrane proteins that are characterized by the presence of four transmembrane domains. They are widely expressed in various tissues and cells, where they play important roles in regulating cell development, activation, motility, and fusion. Tetraspanins can interact with other membrane proteins, such as integrins, receptors, and enzymes, to form complexes that function in signal transduction, trafficking, and adhesion. They also participate in the regulation of various cellular processes, including cell proliferation, differentiation, survival, and apoptosis. Some tetraspanins have been implicated in the pathogenesis of various diseases, such as cancer, autoimmune disorders, and viral infections.
Membrane glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. They are integral components of biological membranes, spanning the lipid bilayer and playing crucial roles in various cellular processes.
The glycosylation of these proteins occurs in the endoplasmic reticulum (ER) and Golgi apparatus during protein folding and trafficking. The attached glycans can vary in structure, length, and composition, which contributes to the diversity of membrane glycoproteins.
Membrane glycoproteins can be classified into two main types based on their orientation within the lipid bilayer:
1. Type I (N-linked): These glycoproteins have a single transmembrane domain and an extracellular N-terminus, where the oligosaccharides are predominantly attached via asparagine residues (Asn-X-Ser/Thr sequon).
2. Type II (C-linked): These glycoproteins possess two transmembrane domains and an intracellular C-terminus, with the oligosaccharides linked to tryptophan residues via a mannose moiety.
Membrane glycoproteins are involved in various cellular functions, such as:
* Cell adhesion and recognition
* Receptor-mediated signal transduction
* Enzymatic catalysis
* Transport of molecules across membranes
* Cell-cell communication
* Immunological responses
Some examples of membrane glycoproteins include cell surface receptors (e.g., growth factor receptors, cytokine receptors), adhesion molecules (e.g., integrins, cadherins), and transporters (e.g., ion channels, ABC transporters).
Uroplakins are a group of proteins found in the urothelium, which is the tissue that lines the urinary tract. These proteins are specifically located in the apical surface of the urothelial cells, where they form part of the asymmetric unit membrane (AUM) and play a crucial role in maintaining the barrier function of the urothelium. Uroplakins are organized into large complexes called uroplakin plaques, which cover approximately 70-80% of the apical surface of superficial urothelial cells. There are four major types of uroplakins, known as uroplakin Ia, Ib, II, and III, each with distinct structural and functional properties. Mutations in genes encoding uroplakins have been associated with certain bladder diseases, such as interstitial cystitis and bladder cancer.