Mechanisms of Disease: Involvement of the Urothelium in Bladder Dysfunction
Mechanisms of Disease: Involvement of the Urothelium in Bladder Dysfunction
Although the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.
The urothelium is the epithelial lining of the urinary tract between the renal pelvis and the urinary bladder. Urothelium is composed of at least three layers: 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'. The umbrella cells are interconnected by tight junctions and are covered on their apical surface by crystalline proteins called uroplakins which assemble into hexagonal plaques. Uroplakins and other urothelial cellular differentiation markers, such as cytokeratin 20, are not expressed in the stratified epithelium of the urethra. In some species, the umbrella cells and perhaps also the intermediate cells have projections to the basement membrane. The barrier function of the urothelium is dependent on several features of the umbrella cell layer: these features include tight-junction complexes that reduce the movement of ions and solutes between cells, and specialized lipid molecules and uroplakin proteins in the apical membrane, which reduce the permeability of the cells to small molecules (e.g. water, urea, protons). The apical surface of the urothelium is also covered with a sulfated polysaccharide glycosaminoglycan layer that is thought to act as a nonspecific antiadherence factor and as a defense mechanism against infection.
Although the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.
The urothelium is the epithelial lining of the urinary tract between the renal pelvis and the urinary bladder. Urothelium is composed of at least three layers: 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'. The umbrella cells are interconnected by tight junctions and are covered on their apical surface by crystalline proteins called uroplakins which assemble into hexagonal plaques. Uroplakins and other urothelial cellular differentiation markers, such as cytokeratin 20, are not expressed in the stratified epithelium of the urethra. In some species, the umbrella cells and perhaps also the intermediate cells have projections to the basement membrane. The barrier function of the urothelium is dependent on several features of the umbrella cell layer: these features include tight-junction complexes that reduce the movement of ions and solutes between cells, and specialized lipid molecules and uroplakin proteins in the apical membrane, which reduce the permeability of the cells to small molecules (e.g. water, urea, protons). The apical surface of the urothelium is also covered with a sulfated polysaccharide glycosaminoglycan layer that is thought to act as a nonspecific antiadherence factor and as a defense mechanism against infection.
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