Involvement of STAT3 in bladder smooth muscle hypertrophy following bladder outlet obstruction.
We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness 1 week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between > or = 2.0 and < or = 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (1 Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy.
Fujita
Osamu
O
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Asanuma
Masato
M
Yokoyama
Teruhiko
T
Miyazaki
Ikuko
I
Ogawa
Norio
N
Kumon
Hiromi
H
D000818:Animals; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D051381:Rats; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D001748:Urinary Bladder Neck Obstruction / Q000150:complications*
D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat