Mechanical load increases gene expression of Pdgf Receptor alpha and beta in Bladder smooth muscle cells

Abstract

PURPOSE In previous experiments we have shown a proliferative effect of platelet derived growth factor (PDGF) on smooth muscle cells (SMC) of the bladder of the rat. Thereby the signalling pathway is lipid raft (cholesterol-enriched microdomains) dependent and can be manipulated reversibly by altering membrane cholesterol levels. This study we performed to prove the role of PDGF as a potential regulative mitogen of SMC of the human bladder. MATERIAL AND METHODS Specimens from detrusor and trigone were taken from patients in the course of an ureteral reimplant procedure. Primary SMC-cultures were created. The proliferative effect of growth factors was determined by BrdU incorporation. In select experiments SMC were treated with predefined pressure and stretch for 1 hour. Gene expression was measured by real-time PCR. RESULTS Under full serum conditions both SMC cultures showed different proliferation with a higher growth rate of the trigone. SMC of the trigone showed also a higher proliferation rate in response to the growth factor PDGF. After mechanical load both SMC showed a significant increase in gene expression of PDGF receptor (PDGFR) alpha and beta. PDGF itself was not expressed in this SMC. CONCLUSIONS Gene expression of PDGFR after short-term mechanical load of SMC of the bladder supports a regulatory role for PDGF in terms of pressure-induced hypertrophy of the human bladder. Since PDGF is not expressed in SMC, it may act on a paracrinic way with expression in the urothelium. Otherwise in vascular SMC PDGFR is known to be activated in response to stretch, in the absence of PDGF.