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Human bladder as a novel target for vitamin D receptor ligands

Crescioli, C; Morelli, A; Adorini, L; Ferruzzi, P; Luconi, M; Vannelli, GB; Marini, M; Gelmini, S; Fibbi, B and Donati, S, et al. (2005) In Journal of Clinical Endocrinology and Metabolism 90(2). p.962-972
Abstract
Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH... (More)
Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation. (Less)
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publication status
published
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Journal of Clinical Endocrinology and Metabolism
volume
90
issue
2
pages
962 - 972
publisher
The Endocrine Society
external identifiers
  • wos:000226850700055
  • pmid:15572423
  • scopus:20044371821
ISSN
1945-7197
DOI
10.1210/jc.2004-1496
language
English
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yes
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2ba50adf-a741-439f-8f42-9bfc275d25e1 (old id 253603)
date added to LUP
2007-08-14 13:16:01
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@article{2ba50adf-a741-439f-8f42-9bfc275d25e1,
  abstract     = {Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation.},
  author       = {Crescioli, C and Morelli, A and Adorini, L and Ferruzzi, P and Luconi, M and Vannelli, GB and Marini, M and Gelmini, S and Fibbi, B and Donati, S and Villari, D and Forti, G and Colli, E and Andersson, Karl-Erik and Maggi, M},
  issn         = {1945-7197},
  language     = {eng},
  number       = {2},
  pages        = {962--972},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Human bladder as a novel target for vitamin D receptor ligands},
  url          = {http://dx.doi.org/10.1210/jc.2004-1496},
  volume       = {90},
  year         = {2005},
}