Annals of Anatomy - Anatomischer Anzeiger
Volume 198,
March 2015
, Pages 73-82
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Abstract
Over time, much knowledge has been accumulated about the active role of the urothelium, principally in rodents and human. Far from being a mere passive barrier, this specialized epithelium can alter the ion and protein composition of the urine, is able to sense and respond to mechanical stimuli such as pressure, and react to mechanical stimuli by epithelial cell communication with the nervous system. Most of the specialized functions of the urothelium are linked to a number of morpho-physiologic properties exhibited by the superficial umbrella cells, including specialized membrane lipids, asymmetric unit membrane particles and a plasmalemma with stiff plaques which function as a barrier to most substances found in urine, thus protecting the underlying tissues.
Moreover, the entire mucosa lining the low urinary tract, composed of urothelium and sub-urothelium, forms a functional transduction unit, able to respond to eso- and endogenous physical and chemical stimuli in a manner assuring an adequate functional response.
This review will summarize the available information on each area of inquiry from a morpho-functional point of view. Possible considerations pertaining to species of veterinary interest are reviewed as well. The review was prepared consulting the electronic databases PubMed and Cab Abstracts and retrieving all pertinent reports and the relative reference lists, in order to identify any potential additional studies that could be included. Full-length research articles and thematic reviews were considered. Information on the urothelium of some domestic animal species was also included.
Section snippets
Why study the urothelium in domestic animals?
The lower urinary tract (LUT) is highly susceptible to pathologies in all species of veterinary interest. Lower urinary tract diseases (LUTD) in companion animals are well-known to the veterinary surgeon. The damage done in this case is more at an emotional level. In the dog and cat, infections are often asymptomatic, thus, severe tissue lesions might possibly result in more serious diseases without previous clinical and anamnestic signs (Smee et al., 2013). In the livestock species, as for
The layers of the urothelium
The epithelium that lines the urinary tract, including the renal pelvis, ureters, bladder and upper urethra, is so peculiar in morphology and physiology that it cannot be equated with any of the epithelia of classic histology and even merits a special name, which is urothelium or uroepithelium. It has been previously called transitional epithelium, thus signifying its possibility to distend and accommodate large changes in urine volume depending on the filling state of the bladder. It is a
Ion, solute, and water trafficking across the urothelium
Paracellular and transcellular ion, solute, and water transport by the urothelium have been much studied and recently reviewed thoroughly (Khandelwal et al., 2009). Due to the necessity of storing urine with a composition significantly different from that of plasma for protracted periods, the passive permeability of the apical membrane and tight junctions is very low to electrolytes and nonelectrolytes like urea and ammonia (Negrete et al., 1996, Lewis, 2000). Two parallel pathways allow
The sensory web
An urothelium-associated “sensory web” was described by Apodaca et al. (2007) after reviewing the studies of a large mass of researches. A number of receptors/ion channels are present in the urothelium of the rat and other species, including mentioned ENaC, receptors for bradykinin, neurotrophins, purines (P2X and P2Y), protease activated receptors (PARs), amiloride/mechanosensitive Na+ channels and the TRP (Transient Receptor Potential) superfamily of cation channels (TRPV1, TRPV2, TRPV4,
Impact of pathology on urothelial functions
The urothelium together with its underlying sub-urothelium constitute a functional unit able to monitor and respond to external stresses and changing surroundings, with the result of facilitating the urinary tract adjustment to a possibly altered environment. Comprehension of how the urothelium can respond to more abnormal stimuli and how inadequacies of this complex system may contribute to urinary tract disorders is an interesting approach. It has been demonstrated that inflammatory or
Summary and perspectives for veterinary research
The most part of the knowledge about the active role of the urothelium has been accumulating over time in rodents and human. Nonetheless, some areas of research have been covered almost entirely on cultured animal tissues as, for instance, the discovery and description of the asymmetrical unit membrane (AUM), principally achieved on bovine urothelial cells.
Moreover, occurrence of urinary pathologies is widely described in all species of veterinary interest, and some of them show similarities to
Acknowledgements
Personal research mentioned as published articles were funded by the Università degli Studi di Milano, Milan, Italy. The author wish to thank all the co-investigators who have been collaborating with her by collecting the data presented in the cited publications, and in part shown in the figures of this article.
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Cited by (10)
Differential expression of glycans in the urothelial layers of horse urinary bladder
2022, Annals of Anatomy
Citation Excerpt :
Several studies showed that the stratum of intermediate cells closest to the umbrella cell layer is involved in repair of the damaged urothelium. After the loss of umbrella cells which could be a result either of senescence, bacterial infection, or experimental manipulation, the underlying intermediate cells rapidly differentiate into umbrella cells as evidenced by increased expression of uroplakins and gradual formation of well-defined tight junctions, as well as recovery of normal size (Arrighi, 2015; Lavelle et al., 2002). As for the surface cells, the cytoplasm reacted with all the used lectins except for PNA, GSA I-B4, and SBA.
Urothelium is a multilayer epithelium covering the inner surface of the urinary bladder that acts as a blood–urine barrier and is involved in maintaining the wellbeing of the whole organism. Glycans serve in the maturation and differentiation of cells and thus play a key role in the morphology and function of the multilayered epithelium. The aim of the present study was to examine the glycoprotein pattern of the horse urinary bladder urothelium by lectin histochemistry.
The study involved urinary bladders from four horse stallions. Tissue sections were stained with a panel of eleven lectins, in combination with saponification and sialidase digestion (Ks).
Basal cells displayed high-mannose N-glycans (Con A), α2,6-linked sialic acid (SNA), and O-linked sialoglycans with sialic acids linked to Galβl,3GalNAc (T antigen) (KsPNA) and terminal N-acetylgalactosamine (Tn antigen) (KsSBA). The young intermediate cells expressed terminal N-acetylglucosamine (GlcNAc) (GSA II), galactose (GSA I-B4), T- and Tn antigens (PNA, SBA). The mature intermediate cells showed additional high-mannose N-glycans, O-linked sialoglycans (sialyl-T antigen, sialyl-Tn antigen), α2,6- and α2,3-linked sialic acid (MAL II), α1,2-linked fucose (UEA I), and GlcNAc (KsWGA). The latter residue marked the boundary with the overlying surface layer. Few Con A positive intermediate cells were seen to cross the entire urothelium thickness. The surface cells showed additional glycans such as T antigen and sialic acids linked to GalNAc binding DBA (KsDBA). Few surface cells contained α1,3-linked fucose (LTA), whereas some other cells displayed intraluminal secretion of mucin-type glycans terminating with GalNAcα1,3(LFucα1,2)Galβ1,3/4GlcNAcβ1 (DBA). The luminal surface expressed the most complex glycan pattern in the urothelium because only α1,3-linked fucose lacked among the demonstrated glycans.
This study showed that the glycan pattern becomes more complex from the basal to surface layer of the urothelium and that surface cells could modify the composition of urine via the secretion of glycoproteins.
Tissue-engineered PLLA/gelatine nanofibrous scaffold promoting the phenotypic expression of epithelial and smooth muscle cells for urethral reconstruction
2020, Materials Science and Engineering C
Citation Excerpt :
Since the regenerated urethral SMCs could not fill the degraded PLLA scaffold in time, the contractile force of the regenerated urethral smooth muscle tissue was insufficient, which led to urethral stricture. It is well known that the main function of urethral smooth muscle is to maintain urination through contraction [25], and the main function of the urethral epithelium is to ensure that urine passes smoothly through the urethra [26]. In the blank group without scaffold implantation, the degree of urethral stricture was more severe (Fig. S5b).
The repair and regeneration of tissues using tissue-engineered scaffolds represent the ultimate goal of regenerative medicine. Despite rapid developments in the field, urethral tissue engineering methods are still insufficient to replicate natural urethral tissue because the bioactivity of existing scaffolds is inefficient, especially for large tissue defects, which require large tissue-engineered scaffolds. Here, we describe the efficiency of gelatine-functionalized, tubular nanofibrous scaffolds of poly(l-lactic acid) (PLLA) in regulating the phenotypic expression of epithelial cells (ECs) and smooth muscle cells (SMCs) for urethral reconstruction. Flexible PLLA/gelatine tubular nanofibrous scaffolds with hierarchical architecture were fabricated by electrospinning. The PLLA/gelatine nanofibrous scaffold exhibited enhanced hydrophilicity and significantly promoted the adhesion, oriented elongation, and proliferation of New Zealand rabbit autologous ECs and SMCs simultaneously. Compared with pure PLLA nanofibrous scaffold, PLLA/gelatine nanofibrous scaffolds upregulated the expression of keratin (AE1/AE3) in ECs and actin (α-SMA) in SMCs as well as the synthesis of elastin. Three months of in vivo scaffold replacement of New Zealand rabbit urethras indicated that a tubular cellularized PLLA/gelatine nanofibrous scaffold maintained urethral patency and facilitated oriented SMC remodeling, lumen epithelialization, and angiogenesis. Our observations showed the synergistic effects of nano-morphology and biochemical clues in the design of biomimetic scaffolds, which can effectively promote urethral regeneration.
Engineering epithelial-stromal interactions in vitro for toxicology assessment
2017, Toxicology
Citation Excerpt :
These studies together highlight the importance of ESIs for recapitulating oral mucosa for the study of disease phenotypes, toxicology, host-pathogen interactions, and drug permeability. Urinary tract tissues contain a stratified transitional epithelium (urothelium), which is composed of a basal layer of ECs, an intermediate layer of highly proliferative ECs, and a superficial layer of fully differentiated ECs that contain microvilli and form an impenetrable barrier (Arrighi 2015). In vitro tissues to model the urinary bladder, or vesical equivalents, composed of vimentin+ canine oral fibroblasts (basal side) and canine oral keratinocytes (lumenal side) seeded on electrospun silk-fibroin scaffolds exhibited stratified epithelial architecture and promoted urothelial repopulation and wound healing in a urethral defect model, whereas the control cell-free implants elicited no urothelial regeneration at the defect site (Xie et al., 2014).
Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues.
S100A1 expression characterizes terminally differentiated superficial cells in the urothelium of the murine bladder and ureter
2022, Histochemistry and Cell Biology
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In maternal diabetes the placenta is large with abnormal vascular development and increased villous volume. We used a novel stereological 3D power Doppler ultrasound technique to investigate differences in-vivo in the placental fractional volume of power Doppler signal (FrVol-PD) between women with and without diabetes.
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Maintenance of bladder innervation in diabetes: A stereological study of streptozotocin-treated female rats
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Neuropathy and cystopathy are two common conditions in patients with chronic diabetes. Despite obvious bladder sensory and motor nerve dysfunction in diabetes, no studies have selectively explored whether sensory or motor innervation is affected in the bladder. In the present study, we tested the hypothesis that loss of bladder sensory and motor fibers is responsible for bladder sensory and motor dysfunction. Parasympathetic and sensory innervation of the bladder dome and neck were examined using immunohistochemistry (IHC) and stereology in adult female rats 12weeks after induction of diabetes by streptozotocin. Naïve and age matched rats were evaluated as controls. Diabetic rats had mean blood glucose level of >400mg/dl, and bladder weights and thicknesses that were more than doubled compared to naïve rats. In naïve rats, parasympathetic vesicular acetylcholine transporter (VAT) and sensory calcitonin gene-related peptide (CGRP) immunopositive nerve fibers were located in bladder smooth muscle and were more densely distributed in the neck compared to the dome. Within the urothelial region, CGRP nerve fibers were densely distributed while VAT nerve fibers were sparsely distributed in the bladder neck and both were virtually absent in the bladder dome. Streptozotocin induced diabetes did not change the total nerve fiber length of either VAT or CGRP stained fibers in either the neck or dome. These studies indicate that hyperglycemia, induced by streptozotocin treatment, does not result in a loss of parasympathetic VAT or CGRP sensory nerve fibers, per se, but the doubling of bladder weight and mass does indicate a decrease in innervation density.
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We sought to determine whether women with overactive bladder who required third line therapy would demonstrate greater central sensitization, indexed by temporal summation to heat pain stimuli, than those with overactive bladder.
We recruited 39 women with overactive bladder from the urology clinic who were planning to undergo interventional therapy for medication refractory overactive bladder with onabotulinumtoxinA bladder injection or sacral neuromodulation. We also recruited 55 women with overactive bladder who were newly seen at our urology clinic or who responded to advertisements for study participation. Participants underwent quantitative sensory testing using a thermal temporal summation protocol. The primary study outcome was the degree of temporal summation as reflected in the magnitude of positive slope of the line fit to the series of 10 stimuli at a 49C target temperature. We compared the degree of temporal summation between the study groups using linear regression.
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FAQs
What is the function of the urothelium in the bladder? ›
The urothelium represents the first line of bladder defense and an interface between pathogens and defense mechanisms. Functions of the urothelium include control of permeability, immune responses and cell-cell communication, which seems to play a pivotal role in responding to injuries and infections.
What is the urothelium also known as? ›The urothelium reorganizes into two or three layers in the distended bladder without structural damage. Due to this transitional ability of the urothelium, it is also known as the transitional epithelium.
What are the two types of umbrella cells found in the urothelium? ›The urothelium consists of three cell types: basal, intermediate, and superficial cells, also known as umbrella cells or facet cells8. The basal cells are the most undifferentiated urothelial cell type, located at the basement membrane of the lumen and serving a progenitor role.
How is urothelium adapted for its function? ›The urothelium is adapted as a barrier epithelium through: Specialised features that limit transcellular and paracellular permeability. Longevity of superficial urothelial cells to preserve urinary barrier function. High threshold for apoptosis - where cell repair rather than loss is the default pathway.
Why is urothelium important? ›The urothelium is a highly specialized type of tissue that lines the inside of your urinary tract. It serves as a barrier, preventing urine (pee) from leaking out into your body. It also stretches and contracts as your bladder fills and empties.
What is the function of urothelium quizlet? ›What is the urothelium of the bladder? Multilayered epithelium. Apical (umbrella cells). Functions include: Barrier, afferent signaling.
What is the structure of the urothelium? ›The urothelium is a transitional epithelial tissue, composed of at least three layers (FIGURE 2A): a basal cell layer attached to a basement membrane, an intermediate layer, and a superficial or apical layer composed of large hexagonal cells (diameters of 25–250 μm) known as “umbrella cells” (20, 158).
What type of cells are urothelium? ›Urothelial cells (UC) are classified as transitional epithelium, and they cover almost the entire luminal surface of the urinary tract. This includes the renal pelvis, ureters, bladder, and the proximal segment of the urethra. Urothelium provides a robust permeability barrier across the urinary tract.
Is urothelial the same as bladder? ›Urothelial (transitional cell) bladder cancer
About 90 out of 100 bladder cancers in the UK (about 90%) are urothelial cancer. These are also called transitional cell cancer. Urothelial cancer develops from the cells of the bladder lining (urothelium). These are called transitional or urothelial cells.
The urothelium is a unique, highly specialized epithelium lining the lower urinary tract. It has a variable number of cell layers, but in the rodent urinary bladder it is usually three cell layers thick in the urinary bladder and more in the ureter.
What are the layers of urothelium? ›
The urothelium is a stratified epithelium comprised of three distinct cell layers: the superficial layer, populated by a single layer of umbrella cells; the intermediate cell layer, which can be one-to-several layers thick depending on species; and the basal cell layer, which is one cell layer thick (295) (FIGURE 1A).
Which cell junction is present in urothelium? ›This is the only cell layer of the urothelium that forms identifiable tight junctions and adherens junctions, specialized regions of cell-cell contact that seal the intercellular space between adjacent epithelial cells (see discussion in sects.
What is the urothelium derived from? ›Urothelium in the upper urinary tract is derived from the embryonic mesodermal germ layer, while urothelium in the lower urinary tract (LUT) originates in the endodermal germ layer.
What are the reactive changes in the urothelium? ›Reactive Urothelial Atypia
Increased nuclear size, vesicular appearing chromatin, and pinpoint nucleoli are the most common features identified microscopically with reactive changes, which often occur in the presence of an inflammatory infiltrate within the urothelium (Fig.
Layers of the bladder wall
The urothelium is also called the transitional epithelium. The lamina propria (also called the submucosa) is a thin layer of connective tissue that surrounds the urothelium. It contains blood vessels, nerves and glands.
If intelligence is considered to be a reflection of a biological system which alters its output in response to changing surroundings, with the object of allowing the organism to adjust to this altered environment, then the urothelium, like any sensory system may be considered intelligence.
What is an example of transitional epithelium or urothelium? ›Transitional Epithelium Examples
The transitional epithelium, also known as the urothelium, lines the urethra, ureters, and urinary bladder. The transitional epithelium that lines the prostatic urethra of the male reproductive system is connected with the urothelium of the urinary bladder.
Urothelium is a specialized epithelium that lines most of the urinary tract including the renal pelvis, ureter, bladder, and proximal urethra.
What is epithelial dysfunction of the bladder urothelium? ›In interstitial cystitis (IC), disruption of the urothelial barrier may initiate a cascade of events in the bladder, leading to symptoms and disease. Specifically, epithelial dysfunction leads to the migration of urinary solutes, in particular, potassium, that depolarize nerves and muscles and cause tissue injury.
What organs have urothelial cells? ›Urothelium or transitional epithelium.
This is the layer of cells that lines the inside of the kidneys, ureters, bladder, and urethra. Cells in this layer are called urothelial cells or transitional cells.
Where are urothelial cells found? ›
Bladder cancer most often begins in the cells (urothelial cells) that line the inside of your bladder. Urothelial cells are also found in your kidneys and the tubes (ureters) that connect the kidneys to the bladder. Urothelial cancer can happen in the kidneys and ureters, too, but it's much more common in the bladder.
Are all bladder cancers urothelial? ›Urothelial carcinoma (also called transitional cell carcinoma) is cancer that begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs. Almost all bladder cancers are urothelial carcinomas.
Does everyone have urothelial cells? ›Urothelial cells are present in all urine specimens and exfoliate readily from tumors of the urothelial lining. Urine cytology is therefore an important primary method of diagnosing urothelial tumors, and in combination with cytoscopy and biopsy, it is used as an adjunct.
Can you live without a bladder? ›Can a person live without a bladder? Yes, you can live without a bladder, but you'll need a new reservoir to hold pee that your kidneys produce. However, if a surgeon removes your entire bladder, there's an adjustment period as you become more comfortable with a new way to relieve yourself.
How thick is the urothelium? ›Normal urothelium - UpToDate. The normal urothelium is composed of three to seven cell layers; the thickness varies depending on the extent of bladder distension. Normal urothelial cells are approximately two to three times the size of stromal lymphocytes.
What are rare urothelial cells? ›Atypical urothelial cells: This means that the pathologist found some abnormalities in your urine sample, but the cells weren't abnormal enough to be considered cancer. Suspicious for high-grade urothelial carcinoma: This means that the pathologist found abnormal cells in your urine sample that might be cancer.
Why are tight junctions present in urothelium? ›Tight junctions (TJs) are essential for normal function of epithelia, restricting paracellular diffusion and contributing to the maintenance of cell surface polarity. Superficial cells of the urothelium develop TJs, the basis for the paracellular permeability barrier of the bladder against diffusion of urinary solutes.
What is the name of the muscle that controls the bladder? ›The wall of the bladder is comprised of smooth muscle fibers oriented in multiple different directions. These smooth muscle fibers are collectively known as the detrusor muscle. This interwoven orientation provides the bladder with the ability to stretch in response to the presence of urine.
What is the function of the urothelium in the renal pelvis? ›Urothelium is a specialized epithelium that lines most of the urinary tract including the renal pelvis, ureter, bladder, and proximal urethra. Urothelium is known to play a key role in membrane permeability, modulating surface area and mediating host response to infection [7–10].
What is an example of urothelium? ›Transitional epithelium lines the organs of the urinary system and is known here as urothelium. The bladder for example has a need for great distension. Transitional epithelium of the urinary bladder, known as urothelium.
What does it mean to have benign urothelial cells? ›
A non-cancerous (benign) tumour of the bladder is a growth that starts in the lining or other tissues of the bladder. A non-cancerous condition is when there is a change to bladder cells. Non-cancerous tumours and conditions do not spread (metastasize) to other parts of the body.
Does everyone have urothelial cells in urine? ›Urothelial cells are present in all urine specimens and exfoliate readily from tumors of the urothelial lining. Urine cytology is therefore an important primary method of diagnosing urothelial tumors, and in combination with cytoscopy and biopsy, it is used as an adjunct.
What is the urothelium made of? ›The urothelium is a stratified epithelium comprised of three distinct cell layers: the superficial layer, populated by a single layer of umbrella cells; the intermediate cell layer, which can be one-to-several layers thick depending on species; and the basal cell layer, which is one cell layer thick (295) (FIGURE 1A).
Are most bladder tumors benign or malignant? ›While the majority of bladder tumors are cancerous, there are benign bladder tumors. Some of these benign tumors have a similar appearance to malignant tumors, so the role of biopsy remains very important. Some examples of benign bladder tumors include a bladder papilloma and a nephrogenic adenoma.
Do benign bladder tumors need to be removed? ›However, some benign masses can bleed or grow very large and cause problems by taking up too much space in your bladder or pressing on other organs in your body. In that case, we usually remove or treat benign masses, using a TURBT procedure.
Is urothelial carcinoma malignant or benign? ›This divides bladder cancers into 4 groups: urothelial papilloma means it is a non cancerous (benign) tumour. papillary urothelial neoplasm of low malignant potential (PUNLMP) means it is a very slow growing tumour that is unlikely to spread.