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Acyloxyacyl hydrolase regulates voiding activity.

Authors
  • Aguiniga, Lizath M1
  • Searl, Timothy J2
  • Rahman-Enyart, Afrida1
  • Yaggie, Ryan E1
  • Yang, Wenbin1
  • Schaeffer, Anthony J1
  • Klumpp, David J1, 3
  • 1 Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • 2 Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • 3 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Type
Published Article
Journal
AJP Renal Physiology
Publisher
American Physiological Society
Publication Date
Apr 01, 2020
Volume
318
Issue
4
Identifiers
DOI: 10.1152/ajprenal.00442.2019
PMID: 32003596
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Corticotropin-releasing factor (CRF) regulates diverse physiological functions, including bladder control. We recently reported that Crf expression is under genetic control of Aoah, the locus encoding acyloxyacyl hydrolase (AOAH), suggesting that AOAH may also modulate voiding. Here, we examined the role of AOAH in bladder function. AOAH-deficient mice exhibited enlarged bladders relative to wild-type mice and had decreased voiding frequency and increased void volumes. AOAH-deficient mice had increased nonvoiding contractions and increased peak voiding pressure in awake cystometry. AOAH-deficient mice also exhibited increased bladder permeability and higher neuronal firing rates of bladder afferents in response to stretch. In wild-type mice, AOAH was expressed in bladder projecting neurons and colocalized in CRF-expressing neurons in Barrington's nucleus, an important brain area for voiding behavior, and Crf was elevated in Barrington's nucleus of AOAH-deficient mice. We had previously identified aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor-γ as transcriptional regulators of Crf, and conditional knockout of AhR or peroxisome proliferator-activated receptor-γ in Crf-expressing cells restored normal voiding in AOAH-deficient mice. Finally, an AhR antagonist improved voiding in AOAH-deficient mice. Together, these data demonstrate that AOAH regulates bladder function and that the AOAH-Crf axis is a therapeutic target for treating voiding dysfunction.

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