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Am J Physiol Renal Physiol (August 6, 2002). doi:10.1152/ajprenal.00168.2002
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Articles in PresS, published online ahead of print August 6, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00168.2002
Submitted on May 1, 2002
Accepted on July 15, 2002

Mechanical Stretch Regulates Cell Survival In Human Bladder Smooth Muscle Cells In Vitro

David J. Galvin1, R. William G. Watson1*, James I. Gillespie2, Hugh R. Brady3, and John M. Fitzpatrick1

1 Department of Surgery, Mater Misericordiae Hospital, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
2 Department of Reproductive and Surgical Sciences, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom
3 Department of Medicine and Therapeutics, Mater Misericordiae Hospital, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

* To whom correspondence should be addressed. E-mail: research{at}profsurg.iol.ie.

Our understanding of the pathophysiology of the overactive bladder is poor. It has been proposed that localised contractions result in the abnormal stretching of bladder smooth muscle. We hypothesise that stretch regulates the cellular processes that determine tissue size. The aims of this study were to investigate the effect of stretch on apoptosis, proliferation, cell hypertrophy and growth factor production in human bladder smooth muscle cells in vitro. Normal human detrusor muscle was obtained from patients undergoing radical cystectomy for invasive bladder cancer, and primary cultures were established. Cells were mechanically stretched on flexible plates at a range of pressures and times. Apoptosis was assessed by Propidium Iodide Incorporation and flow cytometry. Radiolabelled thymidine and amino acid incorporation were used to assess proliferation and cell hypertrophy. ELISA and RT-PCR was used to assess growth factor production. Mechanical stretch inhibits apoptosis in a time and dose dependent manner and was associated with increases in the anti-apoptotic proteins HSP 70 and cIAP-1. Stretch also increases smooth muscle cell proliferation and hypertrophy, but hypertrophy is the more dominant response. These changes were associated with increases in IGF-1 and bFGF, and a decrease in TGFß-1. Mechanical stretch regulates apoptosis, proliferation and cell hypertrophy in human bladder smooth muscle cells.




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