BXL‐628, a vitamin D receptor agonist effective in benign prostatic hyperplasia treatment, prevents RhoA activation and inhibits RhoA/Rho kinase signaling in rat and human bladder
2006; Wiley; Volume: 67; Issue: 3 Linguagem: Inglês
10.1002/pros.20463
ISSN1097-0045
AutoresAnnamaria Morelli, Linda Vignozzi, Sandra Filippi, Gabriella Barbara Vannelli, Stefano Ambrosini, Rosa Mancina, Clara Crescioli, Silvia Donati, Benedetta Fibbi, Enrico Colli, Luciano Adorini, Mario Maggi,
Tópico(s)Hormonal and reproductive studies
ResumoAbstract BACKGROUND BXL‐628 is a calcitriol analog shown to decrease prostate growth in preclinical and clinical studies. BPH symptoms are generated not only by prostate overgrowth but also by bladder overactivity, resulting from an increased RhoA/Rho‐kinase signaling. Because bladder smooth muscle cells express VDR, we studied effects of BXL‐628 on this pathway. METHODS RhoA and Rho‐kinase gene expression and functional activity were studied in rat and human bladder smooth muscle by real‐time RT‐PCR, immuno‐kinase assays, western blot analysis, confocal microscopy, in vitro contractility, and cell migration. RESULTS In bladder smooth muscle, carbachol responsiveness was delayed and Rho‐kinase activity reduced by BXL‐628 treatment because of impaired RhoA membrane translocation and activation. Accordingly, RhoA‐mediated biological functions, such as cell migration and cytoskeleton remodeling were also inhibited by BXL‐628. CONCLUSIONS BXL‐628 inhibits RhoA/Rho‐kinase signaling, a calcium sensitizing pathway, suggesting its possible clinical use in the treatment of altered bladder contractility often associated with BPH‐induced lower urinary tract symptoms. Prostate 67:234–247, 2007. © 2006 Wiley‐Liss, Inc.
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