Cellular basis of urothelial squamous metaplasia

Abstract

Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

In Vivo Disruption of an Rb–E2F–Ezh2 Signaling Loop Causes Bladder Cancer

“…This is in contrast with the absence of bladder tumors upon Rb1 ablation in the urothelium (13). In this regard, we did not observe bladder tumor development in large cohorts of mice bearing the specific elimination of Rb gene directed by keratin K14cre expression (14), which is active in the adult mouse urothelium (15), even in the absence of p107 (16), E2F1 (17) or p130 (18). These data indicate the existence of large overlapping roles for the Rb family members in bladder urothelial cells, similar to the reported for other mouse epithelial cells (19).…”

Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection

“…Thus, the Wolffian ducts have been shown to undergo apoptosis during ureteral transposition and therefore do not contribute to trigone formation (7). Instead, a number of recent mouse models and tissue-transposition studies (7, 8), as well as in vitro studies of urothelial cells (9), suggest that the trigone is endodermal in origin. In males, the bladder base rests on the endopelvic fascia and the pelvic floor musculature, and the bladder neck is 3 to 4 cm behind the symphysis pubis and is fixed by the endopelvic fasciae and the prostate.…”

“…Although the term urothelium has been used to describe the epithelia covering the mucosal surfaces of the bulk of the urinary tract, which share the expression of a group of integral membrane proteins called uroplakins, recent data indicate that the urothelia of the ureters, bladder, and possibly other areas are distinguishable with respect to the detailed morphological and biochemical features, their in vitro proliferative behaviors when placed under identical tissue-culture conditions, and their embryological origin. For example, it has been shown that ureteral urothelium contains lower amounts of uroplakins and fewer cytoplasmic fusiform vesicles than bladder urothelium (9, 14, 15). It is now clear that these phenotypic differences are due to intrinsic divergence instead of extrinsic modulation (9).…”

“…For example, it has been shown that ureteral urothelium contains lower amounts of uroplakins and fewer cytoplasmic fusiform vesicles than bladder urothelium (9, 14, 15). It is now clear that these phenotypic differences are due to intrinsic divergence instead of extrinsic modulation (9). These findings are consistent with the fact that the renal pelvic and ureteral urothelia are derived from the mesoderm, whereas bladder and urethral urothelia are derived from the endoderm.…”

“…In addition to the bladder, UPIa has been found on the mucosal surfaces of the ureters, renal pelvis, and major and minor calyces (9, 14). It has been proposed that interaction of the FimH adhesin of type 1-fimbriated UPEC with UPIa at these locations help bacteria resist the flow of urine and, coupled with bacterial flagella formation, may facilitate the ascent of bacteria from the bladder into the upper urinary tract (16, 37).…”