Role of PAR2 in the Development of Lower Urinary Tract Dysfunction.
J Urol
; 196(2): 588-98, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-26860791
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prostatite
/
Dor Pélvica
/
Receptor PAR-2
/
Dor Crônica
/
Sintomas do Trato Urinário Inferior
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Urol
Ano de publicação:
2016
Tipo de documento:
Article