Beyond neurons: Involvement of urothelial and glial cells in bladder function.
Authors Birder LA, Wolf-Johnston AS, Chib MK, Buffington CA, Roppolo JR, Hanna-Mitchell
Submitted By Lori Birder on 3/31/2010
Status Published
Journal Neurourology and urodynamics
Year 2010
Date Published 2/1/2010
Volume : Pages 29 : 88 - 96
PubMed Reference 20025015
Abstract AIM: The urothelium, or epithelial lining of the lower urinary tract (LUT), is
likely to play an important role in bladder function by actively communicating
with bladder nerves, smooth muscle, and cells of the immune and inflammatory
systems. Recent evidence supports the importance of non-neuronal cells that may
extend to both the peripheral and central processes of the neurons that transmit
normal and nociceptive signals from the urinary bladder. Using cats diagnosed
with a naturally occurring syndrome termed feline interstitial cystitis (FIC),
we investigated whether changes in physiologic parameters occur within 3 cell
types associated with sensory transduction in the urinary bladder: 1) the
urothelium, 2) identified bladder dorsal root ganglion (DRG) neurons and 3) grey
matter astrocytes in the lumbosacral (S1) spinal cord. As estrogen fluctuations
may modulate the severity of many chronic pelvic pain syndromes, we also
examined whether 17beta-estradiol (E2) alters cell signaling in rat urothelial
cells. RESULTS: We have identified an increase in nerve growth factor (NGF) and
substance P (SP) in urothelium from FIC cats over that seen in urothelium from
unaffected (control) bladders. The elevated NGF expression by FIC urothelium is
a possible cause for the increased cell body size of DRG neurons from cats with
FIC, reported in this study. At the level of the spinal cord, astrocytic GFAP
immuno-intensity was significantly elevated and there was evidence for
co-expression of the primitive intermediate filament, nestin (both indicative of
a reactive state) in regions of the FIC S1 cord (superficial and deep dorsal
horn, central canal and laminae V-VIl) that receive input from pelvic afferents.
Finally, we find that E2 triggers an estrus-modifiable activation of p38 MAPK in
rat urothelial cells. There were cyclic variations with E2-mediated elevation of
p38 MAPK at both diestrus and estrus, and inhibition of p38 MAPK in proestrous
urothelial cells. CONCLUSION: Though urothelial cells are often viewed as
bystanders in the processing of visceral sensation, these and other findings
support the view that these cells function as primary transducers of some
physical and chemical stimuli. In addition, the pronounced activation of spinal
cord astrocytes in an animal model for bladder pain syndrome (BPS) may play an
important role in the pain syndrome and open up new potential approaches for
drug intervention.

Investigators with authorship
Lori BirderUniversity of Pittsburgh Medical Center-Health System


Mapk14mitogen activated protein kinase 14
Ngfnerve growth factor