Stover Joshua, Nagatomi Jiro
Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, SC 29634-0905, USA.
Ann Biomed Eng. 2007 Sep;35(9):1585-94. doi: 10.1007/s10439-007-9331-9. Epub 2007 May 24.
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.
先前的研究表明，脊髓损伤后膀胱会出现严重的组织重塑。在这种病理性膀胱中，不受抑制的非排尿收缩使膀胱细胞承受膀胱内压的周期性振荡。我们假设周期性压力是膀胱过度活动症中组织重塑的潜在触发因素。使用定制装置，将体外培养的大鼠膀胱平滑肌细胞（SMC）暴露于频率为0.1 Hz或0.02 Hz的周期性静水压力（40 cm H₂O）下长达24小时。与静态对照和暴露于0.02 Hz周期性压力的细胞相比，暴露于0.1 Hz周期性压力的SMC中DNA含量显著更高（p < 0.05）。我们证实DNA的增加是由于细胞增殖增加，这由BrdU掺入增加表明，而不是由于对周期性压力的凋亡率降低。此外，暴露于周期性压力后SMC中Akt磷酸化显著升高（p < 0.05），并且在存在PI3K抑制剂渥曼青霉素和LY294002的情况下缺乏压力诱导的SMC增生，这表明PI3K/Akt途径参与了SMC对周期性压力的增殖反应。我们得出结论，长期暴露于膀胱内压振荡可能是膀胱组织重塑的潜在触发因素。
