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Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction

Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and... Bladder Outlet Obstruction (BOO) is ultimately experienced by ≈90% of men, most commonly secondary to benign prostatic hyperplasia. Inflammation is a critical driver of BOO pathology in the bladder and can be divided into two critical steps; initiation and resolution. While great strides have been made toward understanding initiation of inflammation in the bladder (through the NLRP3 inflammasome), no studies have examined resolution. Resolution is controlled by 5 classes of compounds known as Specialized Pro-resolving Mediators (SPMs), all of which bind to one or more of 7 different receptors. Using immunocytochemistry, we show the presence of 6 of the known SPM receptors in the bladder of control and BOO rats; the 7th has no rodent homolog. The expression was predominantly localized to the urothelia, often with some expression in the smooth muscle, but little to none in the interstitial cells. We next examined the therapeutic potential of the Annexin-A1 resolution system, also present in control and BOO bladders. Using the peptide mimetic Ac2-26, we blocked inflammation-initiating pathways (NLRP3 activation), diminished BOO-induced inflammation (Evans blue dye extravasation), and normalized bladder dysfunction (urodynamics). Excitingly, Ac2-26 also promoted faster and more complete functional recovery after surgical de-obstruction. Together, the results demonstrate that the bladder expresses a wide variety of potential pro-resolving pathways and that modulation of just one of these pathways can alleviate many detrimental aspects of BOO and speed recovery after de-obstruction. This work establishes a precedent for future studies evaluating SPM effectiveness in resolving the many conditions associated with bladder inflammation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Physiology-Renal Physiology The American Physiological Society

Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction

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References (62)

ISSN
1931-857x
eISSN
1522-1466
DOI
10.1152/ajprenal.00205.2021
Publisher site
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Abstract

Bladder Outlet Obstruction (BOO) is ultimately experienced by ≈90% of men, most commonly secondary to benign prostatic hyperplasia. Inflammation is a critical driver of BOO pathology in the bladder and can be divided into two critical steps; initiation and resolution. While great strides have been made toward understanding initiation of inflammation in the bladder (through the NLRP3 inflammasome), no studies have examined resolution. Resolution is controlled by 5 classes of compounds known as Specialized Pro-resolving Mediators (SPMs), all of which bind to one or more of 7 different receptors. Using immunocytochemistry, we show the presence of 6 of the known SPM receptors in the bladder of control and BOO rats; the 7th has no rodent homolog. The expression was predominantly localized to the urothelia, often with some expression in the smooth muscle, but little to none in the interstitial cells. We next examined the therapeutic potential of the Annexin-A1 resolution system, also present in control and BOO bladders. Using the peptide mimetic Ac2-26, we blocked inflammation-initiating pathways (NLRP3 activation), diminished BOO-induced inflammation (Evans blue dye extravasation), and normalized bladder dysfunction (urodynamics). Excitingly, Ac2-26 also promoted faster and more complete functional recovery after surgical de-obstruction. Together, the results demonstrate that the bladder expresses a wide variety of potential pro-resolving pathways and that modulation of just one of these pathways can alleviate many detrimental aspects of BOO and speed recovery after de-obstruction. This work establishes a precedent for future studies evaluating SPM effectiveness in resolving the many conditions associated with bladder inflammation.

Journal

American Journal of Physiology-Renal Physiology – The American Physiological Society

Published: Oct 1, 2021

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