ROLE OF BASIC FIBROBLAST GROWTH FACTOR IN THE NEUROPATHIC BLADDER PHENOTYPE

Abstract

The neuropathic bladder is characterized by increased muscle mass within the bladder wall and reduced functional capability. The exact cellular mechanisms that regulate these changes have yet to be elucidated. We determine the role of basic fibroblast growth factor (bFGF) in the increased smooth muscle cell (SMC) proliferation seen in the neuropathic bladder. Primary human bladder SMC cultures were established from patients with either normal or neuropathic bladders (3 each). Expression of bFGF, smooth muscle markers and bFGF receptor-1 were quantified by immunohistochemistry and Western blot analysis. Cell proliferation was assayed by cell count after stimulation with recombinant bFGF in the presence and absence of a neutralizing anti-bFGF antibody. Neuropathic bladder SMC expressed higher levels of bFGF than normal bladder SMC. Functional studies using exogenous bFGF demonstrated a significant dose dependent increase in cell proliferation in normal and neuropathic bladder SMC. This stimulatory effect could be completely inhibited by simultaneous addition of anti-bFGF antibodies. Also, the higher rate of baseline cell proliferation in neuropathic bladder SMC could be brought down to normal levels after treatment with anti-bFGF antibodies. The addition of exogenous bFGF showed no effect on the expression of fibroblast growth factor receptor-1 or smooth muscle phenotypic markers, suggesting that bFGF induces cell proliferation in neuropathic bladders in an autocrine fashion. These novel findings support the hypothesis that bFGF is over expressed in the neuropathic bladder and directly influences an increase in SMC proliferation.