Role of PAR2 in the Development of Lower Urinary Tract Dysfunction

Kenny Roman, Stephen F. Murphy, Joseph D. Done, Kevin E. McKenna, Anthony J. Schaeffer, Praveen Thumbikat*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. Materials and Methods Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. Results Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. Conclusions PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.

Original languageEnglish (US)
Pages (from-to)588-598
Number of pages11
JournalJournal of Urology
Volume196
Issue number2
DOIs
StatePublished - Aug 1 2016

Fingerprint

Prostatitis
Urinary Tract
Urinary Bladder
Prostate
Chronic Pain
Pelvic Pain
Suspensions
Spleen
Lymph Nodes
PAR-2 Receptor
Tryptases
Lower Urinary Tract Symptoms
Urodynamics
Collagen Type I
Immunoblotting
Knockout Mice
Smooth Muscle
Actins
Flow Cytometry
Fibrosis

Keywords

  • fibrosis
  • lower urinary tract symptoms
  • pain
  • prostatitis
  • receptor, PAR-2

ASJC Scopus subject areas

  • Urology

Cite this

@article{6fbc35f1158a4befac1685413e24289b,
title = "Role of PAR2 in the Development of Lower Urinary Tract Dysfunction",
abstract = "Purpose Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. Materials and Methods Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. Results Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. Conclusions PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.",
keywords = "fibrosis, lower urinary tract symptoms, pain, prostatitis, receptor, PAR-2",
author = "Kenny Roman and Murphy, {Stephen F.} and Done, {Joseph D.} and McKenna, {Kevin E.} and Schaeffer, {Anthony J.} and Praveen Thumbikat",
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Role of PAR2 in the Development of Lower Urinary Tract Dysfunction. / Roman, Kenny; Murphy, Stephen F.; Done, Joseph D.; McKenna, Kevin E.; Schaeffer, Anthony J.; Thumbikat, Praveen.

In: Journal of Urology, Vol. 196, No. 2, 01.08.2016, p. 588-598.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of PAR2 in the Development of Lower Urinary Tract Dysfunction

AU - Roman, Kenny

AU - Murphy, Stephen F.

AU - Done, Joseph D.

AU - McKenna, Kevin E.

AU - Schaeffer, Anthony J.

AU - Thumbikat, Praveen

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Purpose Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. Materials and Methods Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. Results Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. Conclusions PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.

AB - Purpose Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. Materials and Methods Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. Results Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. Conclusions PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.

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KW - receptor, PAR-2

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