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

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 40 cmH 2O for up to 72 h. 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 40 cmH 2O sustained hydrostatic pressure, while at 20 cmH 2O the effect was minimal until 72 h. 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 40 cmH 2O for up to 72 h 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 24 h exposure to pressures of ≤40 cmH 2O. 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.