Purpose: Fibromuscular tissues of the detrusor/bladder body (B), trigone (T) and ureter (U) display distinct patterns of tissue remodeling in pathologic contexts, however the mechanisms underlying these observations are unknown. In this study we asked whether B, T and U smooth muscle cells (SMC) respond to several SMC growth factors and explored the role of caveolae/lipid raft membrane microdomains in signaling by one of these factors, PDGF-BB. Materials and Methods: SMC were isolated and cultured from B, T and U from newborn rats and from human bladder detrusor. Responses to growth factors were assessed by cell proliferation, DNA synthesis, and immunoblot methods. Cholesterol was depleted from cell membranes in select experiments using cyclodextrin and the cholesterol synthesis inhibitor lovastatin. High-affinity PDGF receptor (PDGFR) sites were measured by 125I-PDGF-BB binding assay. Results: PDGF-BB increased DNA synthesis rate in U and T SMC, with U SMC being highly responsive; in contrast, B SMC did not respond to this growth factor. Two other mitogens, HB-EGF and FGF-2, marginally stimulated DNA synthesis in all lineages. Human detrusor (hD) SMC were also highly responsive to PDGF-BB. Differences in responses to PDGF-BB correlated with translocation of PDGFRs into the caveolae/lipid raft membrane fraction following stimulation, but not with the number of high affinity PDGF binding sites. Cholesterol depletion from cell membranes reduced the response of U and hD SMC to PDGF-BB. Conclusions: These findings indicate that 1) PDGF-BB is likely to be a physiologically relevant stimulator of mitogenic signaling in certain types of urinary tract SMC, 2) there are significant and unanticipated regional differences in the ability of urinary tract SMC to respond to muscle mitogens, and 3) lipid raft membrane microdomains mediate, in part, the ability of urinary tract SMC to respond to PDGF-mediated signals.
- Platelet-derived growth factor
ASJC Scopus subject areas