Smooth muscle hypertrophy following partial bladder outlet obstruction is associated with overexpression of non-muscle caldesmon.
Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, large residual urine volume, and voiding difficulty. We analyzed the expression of smooth muscle-specific caldesmon (h-CaD) and non-muscle (l-CaD) by Western blotting, RT-PCR, and real-time PCR. The expression of l-CaD is increased significantly at the mRNA and protein levels in the decompensated bladders compared to that of normal and compensated bladders. The CaD was also co-localized with myosin containing cytoplasmic fibrils in cells dissociated from obstructed bladders and cultured overnight. Our data show that the inability of decompensated bladders to empty, despite detrusor hypertrophy, is associated with an overexpression of l-CaD. The level of l-CaD overexpression might be a useful marker to estimate the degree of detrusor remodeling and contractile dysfunction in PBOO.
Zhang
Erik Y
EY
Department of Pathobiology and Division of Urology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Stein
Raimund
R
Chang
Shaohua
S
Zheng
Yongmu
Y
Zderic
Stephen A
SA
Wein
Alan J
AJ
Chacko
Samuel
S
D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D001743:Urinary Bladder / Q000473:pathology / Q000502:physiology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism / Q000473:pathology*; D014563:Urodynamics
D015415:Biomarkers; D002148:Calmodulin-Binding Proteins