Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction.
OBJECTIVE
To examine whether the epithelial sodium channel (ENaC) is expressed in the human urinary bladder and how its expression changes in association with outlet obstruction. Detrusor instability occurs in association with bladder outlet obstruction. The increase of afferent activity is one of the possible mechanisms for this detrusor instability. The ENaC expressed in mammals has been implicated in various mechanosensory functions.


METHODS
Specimens of urinary bladder mucosa were obtained from 9 controls and 9 patients with bladder outlet obstruction verified by the International Prostate Symptom Score, prostate volume, and urodynamic tests. In 7 patients with outlet obstruction, involuntary detrusor contraction was demonstrated. The expression and localization of ENaC proteins was examined using immunofluorescent staining. The quantification of ENaC gene expression was assessed by real-time reverse transcriptase-polymerase chain reaction.


RESULTS
The alpha-ENaC, beta-ENaC, and gamma-ENaC proteins were expressed in human urinary bladder epithelium with outlet obstruction, and the alpha-ENaC and gamma-ENaC proteins were virtually unstained in the control bladders. Alpha-ENaC, beta-ENaC, and gamma-ENaC mRNA were detected in 1, 6, and 4 of 9 control bladders, respectively. Each ENaC mRNA was clearly present in all obstructed bladders. The expression levels of each subunit in the obstructed bladders were significantly greater than those in controls. The quantified ENaC expression correlated significantly with the storage symptom score.


CONCLUSIONS
The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction.
Araki
Isao
I
Department of Urology, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Tamaho, Yamanashi, Japan.
Du
Shuqi
S
Kamiyama
Manabu
M
Mikami
Yuki
Y
Matsushita
Kazumichi
K
Komuro
Mitsuo
M
Furuya
Yasuhisa
Y
Takeda
Masayuki
M
D000368:Aged; D000369:Aged, 80 and over; D053503:Epithelial Sodium Channels; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D014549:Urinary Incontinence / Q000209:etiology / Q000378:metabolism*; D014553:Urinary Tract Physiological Phenomena
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels