Urothelial function reconsidered: a new role in urinary protein secretion

Abstract

Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Specifically, we show that normal bovine urothelium synthesizes, as its major differentiation products, 2 well-known proteases, ie, tissue-type plasminogen activator (tPA) and urokinase (uPA), as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP- and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived, rather than kidney derived, as in some other species. This heterogeneity may have evolved in response to different physiologic or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier, but also as a secretor of urinary proteins that can play physiologic or pathologic roles in the urinary tract.