Human Urothelium

Urothelium is the epithelium found lining the bladder and associated urinary tract. It functions as a predominantly impermeable urinary barrier even while accommodating major changes in surface area during bladder filling and voiding. Evolved for this role, urothelium displays many adaptations, exemplified in the highly specialized tight junctions and uroplakin plaques of the urine-facing superficial cells, combined with an exceptional “on-demand” capacity for repair and regeneration. Intrinsic to the specialized nature of urothelium is how proliferation and differentiation are regulated during tissue homeostasis as this can provide unique insight into the drivers, pathways, and emergent phenotypes of urothelial cancer. This chapter looks at developmental and functional features of normal human urothelium that influence its pathogenesis. It considers different experimental platforms available for investigating urothelial biology and highlights some of the differences between urothelia from human and other species. While generally of uncertain significance, these differences can confuse reports and reviews where species derivation is not made evident. Nevertheless, animal models have been instrumental in advancing knowledge as, by enabling study of genetic and molecular mechanisms involved in urothelial development, they have identified key cellular processes and signaling pathways implicated in urothelial form and function. On the other hand, limitations of cross-species comparisons, the massive expansion of human data, and, ultimately, the prize of understanding the specific biology and pathology of human urothelium all fuel interest in alternative in vitro and increasingly computational approaches aimed toward predicting biological processes and responses.