Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation

P. Comeglio, A. K. Chavalmane, B. Fibbi, S. Filippi, M. Marchetta, M. Marini, A. Morelli, G. Penna, L. Vignozzi, G. B. Vannelli, L. Adorini, M. Maggi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH. Aim: To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells. Materials and methods: Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression. Results: Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures. Conclusions: Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.

Original languageEnglish
Pages (from-to)730-738
Number of pages9
JournalJournal of Endocrinological Investigation
Volume33
Issue number10
DOIs
Publication statusPublished - Nov 2010

Keywords

  • BPH
  • Elocalcitol
  • Inflammation
  • RhoA/ROCK
  • Urethra

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation'. Together they form a unique fingerprint.

Cite this