Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.
Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75(NTR), tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75(NTR), and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly (P ≤ 0.01) reduced and p75(NTR) protein expression was significantly (P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Beatrice M
BM
Girard
Susan E
SE
Malley
Margaret A
MA
Vizzard
D000818:Animals; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D020917:Receptor, trkA / Q000378:metabolism / Q000502:physiology; D020813:Receptor, trkB / Q000378:metabolism / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D001743:Urinary Bladder / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014554:Urination / Q000502:physiology; D019459:Urothelium / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB