Cyclic Pressure Stimulates DNA Synthesis through the PI3K/Akt Signaling Pathway in Rat Bladder Smooth Muscle Cells
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Previous studies demonstrated that the bladder exhibited severe tissue remodeling following spinal cord injury. In such pathological bladders, uninhibited non-voiding contractions subject bladder cells to cyclic oscillations of intravesical pressure. We hypothesize that cyclic pressure is a potential trigger for tissue remodeling in overactive bladder. Using a custom-made setup, rat bladder smooth muscle cells (SMC) in vitro were exposed to cyclic hydrostatic pressure (40 cm H2O) at either 0.1 Hz or 0.02 Hz frequency for up to 24 h. When compared to static control and cells exposed to 0.02-Hz cyclic pressure, SMC exposed to 0.1-Hz cyclic pressure contained significantly (p < 0.05) higher amounts of DNA. We confirmed that the increase in DNA was due to increased cell proliferation, indicated by increased BrdU incorporation, but not due to decreased apoptosis rates in response to cyclic pressure. In addition, significant (p < 0.05) elevation of Akt phosphorylation in SMC following exposure to cyclic pressure and lack of pressure-induced SMC hyperplasia in the presence of PI3K inhibitors, wortmannin and LY294002, indicated the involvement of the PI3K/Akt pathway in the proliferative response of SMC to cyclic pressure. We concluded that chronic exposure to intravesical pressure oscillation may be a potential trigger for bladder tissue remodeling.
KeywordsSpinal cord injury Hyperreflexia Mechanotransduction Tissue remodeling
The authors wish to thank Ms. Margaret Gray for assistance with characterization of SMCs and Ms. Cassie Gregory for assistance with cell culture. The authors also wish to thank Dr. Bruce Gao and his laboratory for providing the rats used as source of bladder cells in the present study. The funding for this research was provided by Paralyzed Veterans of America (2289-02) and Clemson University.
- 11.Cross M. J., Stewart A., Hodgkin M. N., Kerr D. J., Wakelam M. J. 1995 Wortmannin and its structural analogue demethoxyviridin inhibit stimulated phospholipase A2 activity in Swiss 3T3 cells. Wortmannin is not a specific inhibitor of phosphatidylinositol 3-kinase. J. Biol. Chem. 270(43):25352–25355PubMedCrossRefGoogle Scholar