Role of Protease-Activated Receptor 2 in the development of lower urinary tract dysfunction

Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We reported that the mast cell-tryptase-PAR2 axis plays a critical role in the development of chronic pain in experimental autoimmune prostatitis (EAP), a mouse model of CP/CPPS.

We therefore examined whether PAR2 activation mediates lower urinary tract dysfunction.

Functional cystometry was used in male B6 mice along with immunoblots and immunohistochemistry for expression of collagen type I alpha I (COL1A1) and alpha-smooth muscle actin (α-SMA). Flow cytometric analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen.

and Conclusions: EAP resulted in increased urinary voiding frequency and decreased bladder capacity thirty days after initiation. Concurrently there was increased expression of collagen type I alpha I (COL1A1) and alpha-smooth muscle actin (α-SMA) in the prostates and bladders. In contrast, induction of EAP in PAR2 KO 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 EAP but PAR2 expression may be required for maintenance of chronic inflammation. Finally, we demonstrated that antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity and attenuated chronic pelvic pain. PAR2 activation in the prostate may thus contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.

The Journal of urology. 2016 Feb 06 [Epub ahead of print]

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

Department of Urology. , Department of Urology. , Department of Urology. , Department of Physiology. , Department of Urology. , Department of Urology; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 

PubMed

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