Urothelial function reconsidered: a role in urinary protein secretion.
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. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, 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 then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological 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 physiological or pathological roles in the urinary tract.
Deng
F M
FM
The Ronald Perelman Department of Dermatology, Kaplan Comprehensive Cancer Center, New York University Medical School, New York, NY 10016, USA.
Ding
M
M
Lavker
R M
RM
Sun
T T
TT
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D015723:Gene Library; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009924:Organ Culture Techniques; D010539:Permeability; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014551:Urinary Tract / Q000737:chemistry / Q000378:metabolism; D014556:Urine / Q000737:chemistry*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism / Q000502:physiology*
D017077:Culture Media, Conditioned; D006023:Glycoproteins; D011257:Pregnancy Proteins; D011506:Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; C021240:tissue-factor-pathway inhibitor 2; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator