Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction.

Vasquez, Evalynn; Cristofaro, Vivian; Lukianov, Stefan; Burkhard, Fiona C.; Hashemi Gheinani, Ali; Monastyrskaya-Stäuber, Katia; Bielenberg, Diane R; Sullivan, Maryrose P; Adam, Rosalyn M (2017). Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction. JCI insight, 2(3), e90617. JCI Insight 10.1172/jci.insight.90617

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Chronic urethral obstruction and the ensuing bladder wall remodeling can lead to diminished bladder smooth muscle (BSM) contractility and debilitating lower urinary tract symptoms. No effective pharmacotherapy exists to restore BSM contractile function. Neuropilin 2 (Nrp2) is a transmembrane protein that is highly expressed in BSM. Nrp2 deletion in mice leads to increased BSM contraction. We determined whether genetic ablation of Nrp2 could restore BSM contractility following obstruction. Partial bladder outlet obstruction (pBOO) was created by urethral occlusion in mice with either constitutive and ubiquitous, or inducible smooth muscle-specific deletion of Nrp2, and Nrp2-intact littermates. Mice without obstruction served as additional controls. Contractility was measured by isometric tension testing. Nrp2 deletion prior to pBOO increased force generation in BSM 4 weeks following surgery. Deletion of Nrp2 in mice already subjected to pBOO for 4 weeks showed increased contractility of tissues tested 6 weeks after surgery compared with nondeleted controls. Assessment of tissues from patients with urodynamically defined bladder outlet obstruction revealed reduced NRP2 levels in obstructed bladders with compensated compared with decompensated function, relative to asymptomatic controls. We conclude that downregulation of Nrp2 promotes BSM force generation. Neuropilin 2 may represent a novel target to restore contractility following obstruction.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Burkhard, Fiona C.; Hashemi Gheinani, Ali and Monastyrskaya-Stäuber, Katia

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2379-3708

Publisher:

JCI Insight

Language:

English

Submitter:

Laetitia Hayoz

Date Deposited:

05 Mar 2018 12:35

Last Modified:

11 Mar 2018 02:22

Publisher DOI:

10.1172/jci.insight.90617

PubMed ID:

28194441

BORIS DOI:

10.7892/boris.109173

URI:

https://boris.unibe.ch/id/eprint/109173

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