Response of bladder smooth muscle cells to obstruction: signal transduction and the role of mechanosensors.
Bladder hypertrophy and detrusor overactivity are well-known bladder responses to outlet obstruction. Mechanical stretch stress is considered the trigger inducing these responses in the urodynamically overloaded bladder. Several studies using an in vitro model of mechanical stress demonstrate that repetitive stretch stimulation of bladder smooth muscle cells results in increased expression of a variety of growth factors and other specific proteins. In the bladder smooth muscle cell, stretch-activated ion channels (SACs) and protein kinase C (PKC) sarcolemmal proteins may function as sensors for external mechanical forces. In particular, SACs couple mechanical stress to activation of c-jun NH2-terminal kinase, which leads to a rapid induction of nuclear transcription factors. PKC also may involve an indirect or direct regulation of nuclear events. In addition, mechanical stress may induce the release of angiotensin II in an autocrine fashion. These factors in turn stimulate expression of specific gene-encoding proteins, such as heparin-binding epidermal growth factor-like growth factor, nerve growth factor, and an isomer of cyclooxygenase-2, all of which have the potential to contribute to structural and functional alterations in the bladder after obstruction.
Yamaguchi
Osamu
O
Department of Urology, Fukushima Medical University, Fukushima City, Fukushima, Japan. yamaosa@cc.fmu.ac.jp
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002478:Cells, Cultured; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007473:Ion Channels; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008465:Mechanoreceptors; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology*
D006133:Growth Substances; D007473:Ion Channels; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases