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

Publication ,  Journal Article
Hughes, FM; Harper, SN; Nosé, BD; Allkanjari, A; Zheng, MT; Jin, H; Purves, JT
Published in: Am J Physiol Renal Physiol
October 1, 2021

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. Although great strides have been made toward understanding the initiation of inflammation in the bladder [through the NLR family pyrin domain containing 3 (NLRP3) inflammasome], no studies have examined resolution. Resolution is controlled by five classes of compounds known as specialized proresolving mediators (SPMs), all of which bind to one or more of the seven different receptors. Using immunocytochemistry, we showed the presence of six of the known SPM receptors in the bladder of control and BOO rats; the seventh SPM receptor has no rodent homolog. Expression was predominantly localized to urothelia, often with some expression in smooth muscle, but little to none in 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 deobstruction. Together, the results demonstrate that the bladder expresses a wide variety of potential proresolving pathways and that modulation of just one of these pathways can alleviate many detrimental aspects of BOO and speed recovery after deobstruction. This work establishes a precedent for future studies evaluating SPM effectiveness in resolving the many conditions associated with bladder inflammation.NEW & NOTEWORTHY To our knowledge, this is the first study of proinflammation-resolving pathways in the bladder, which is the basis of a new pharmacological genus-dubbed "resolution pharmacology" aimed at reducing inflammation without creating an immunocompromised state. Inflammation plays a causative or exacerbating role in numerous bladder maladies. We documented proresolution receptors in the rat bladder and the effectiveness of a specialized proresolving mediator, annexin-A1, in alleviating detrimental aspects of bladder outlet obstruction and speeding recovery after deobstruction.

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Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

October 1, 2021

Volume

321

Issue

4

Start / End Page

F443 / F454

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Urinary Bladder Neck Obstruction
  • Urinary Bladder
  • Rats, Sprague-Dawley
  • Rats
  • Peptides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammation
  • Gene Expression Regulation
  • Female
 

Citation

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Hughes, F. M., Harper, S. N., Nosé, B. D., Allkanjari, A., Zheng, M. T., Jin, H., & Purves, J. T. (2021). Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction. Am J Physiol Renal Physiol, 321(4), F443–F454. https://doi.org/10.1152/ajprenal.00205.2021
Hughes, Francis M., Shelby N. Harper, Brent D. Nosé, Armand Allkanjari, Michael T. Zheng, Huixia Jin, and J Todd Purves. “Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction.Am J Physiol Renal Physiol 321, no. 4 (October 1, 2021): F443–54. https://doi.org/10.1152/ajprenal.00205.2021.
Hughes FM, Harper SN, Nosé BD, Allkanjari A, Zheng MT, Jin H, et al. Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction. Am J Physiol Renal Physiol. 2021 Oct 1;321(4):F443–54.
Hughes, Francis M., et al. “Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction.Am J Physiol Renal Physiol, vol. 321, no. 4, Oct. 2021, pp. F443–54. Pubmed, doi:10.1152/ajprenal.00205.2021.
Hughes FM, Harper SN, Nosé BD, Allkanjari A, Zheng MT, Jin H, Purves JT. Specialized proresolution mediators in the bladder: annexin-A1 normalizes inflammation and bladder dysfunction during bladder outlet obstruction. Am J Physiol Renal Physiol. 2021 Oct 1;321(4):F443–F454.

Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

October 1, 2021

Volume

321

Issue

4

Start / End Page

F443 / F454

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Urinary Bladder Neck Obstruction
  • Urinary Bladder
  • Rats, Sprague-Dawley
  • Rats
  • Peptides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammation
  • Gene Expression Regulation
  • Female