Upregulation of both PDGF-BB and PDGF-BB receptor in human bladder fibroblasts in response to physiologic hydrostatic pressure

Akbal, Cem; Lee, Sang Don; Jung, Chaeyong; Rink, Richard; Kaefer, Martin

doi:10.1016/j.jpurol.2005.08.004

« Previous Next »Journal of Pediatric Urology
Volume 2, Issue 5 , Pages 402-408, October 2006

Upregulation of both PDGF-BB and PDGF-BB receptor in human bladder fibroblasts in response to physiologic hydrostatic pressure☆

Cem Akbal
- Department of Urology, Riley Hospital for Children, Indiana University School of Medicine, Indiana, USA
- Supported by the Scientific and Technical Research Council of Turkey.
Sang Don Lee
- College of Medicine, Pusan National University, Busan, Korea
Chaeyong Jung
- Department of Urology, Riley Hospital for Children, Indiana University School of Medicine, Indiana, USA
Richard Rink
- Department of Urology, Riley Hospital for Children, Indiana University School of Medicine, Indiana, USA
Martin Kaefer
- Department of Urology, Riley Hospital for Children, Indiana University School of Medicine, Indiana, USA
- Corresponding author. Department of Urology, Riley Hospital for Children, Indiana University School of Medicine, 702 Barnhill Drive #1739, Indianapolis, IN 46202, USA. Tel.: +1 317 274 889; fax: +1 317 274 7481.

Received 19 January 2005; accepted 18 August 2005. published online 10 August 2006.

Abstract

Objective

Bladder outlet obstruction can lead to the deposition of extracellular matrix and a resultant decrease in bladder wall compliance. Platelet-derived growth factor (PDGF) is a potent mitogen for fibroblasts and can increase the deposition of extracellular matrix. We attempt to determine if the expression of PDGF-BB and its receptor are altered in human bladder fibroblasts and bladder smooth muscle cells when exposed to hydrostatic pressures in the physiologic range.

Materials and methods

Cultured human bladder fibroblasts and smooth muscle cells were evaluated in vitro by using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 20 and 40cmH₂O for up to 72h. Western blot analyses and RT-PCR were performed to evaluate expression of both PDGF-BB and PDGF-BB receptor.

Results

PDGF-BB and its receptor increased up to 22-fold and 8-fold, respectively, when human bladder fibroblasts were exposed to 40cmH₂O sustained hydrostatic pressure, while at 20cmH₂O the effect was minimal until 72h. mRNA for the PDGF-BB receptor in human bladder fibroblasts increased in comparison to control. Western blot analyses demonstrated that exposure of human bladder smooth muscle cells to a sustained hydrostatic pressure of 20 and 40cmH₂O for up to 72h did not alter expression of either PDGF-BB or its receptor.

Conclusions

Both PDGF-BB and its receptor in human bladder fibroblasts were upregulated in a time- and pressure-dependent manner after as little as 24h exposure to pressures of ≤40cmH₂O. Our results provide support for a potential role of both PDGF-BB and its receptor in bladder fibrosis secondary to increased intravesical pressure. Newer selective PDGF receptor antagonists may prove beneficial in preventing bladder wall fibrosis in patients with either anatomic or functional bladder outlet obstruction.

Keywords: PDGF-BB, PDGF-BB receptor, Bladder fibroblasts, Pressure