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HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model.

Abstract
HMGB1, a nuclear protein, once released to the extracellular space, promotes somatic and visceral pain signals. We thus analyzed the role of HMGB1 in an intravesical substance P-induced bladder pain syndrome (BPS) mouse model. Intravesical administration of substance P caused referred hyperalgesia/allodynia in the lower abdomen and hindpaw without producing severe urothelial damage, which was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin α capable of inactivating HMGB1 and antagonists of RAGE or CXCR4. The HMGB1 inactivation or RAGE blockade also reversed the established bladder pain symptoms. HMGB1 and RAGE are thus considered to serve as therapeutic targets for BPS.
AuthorsYuhei Irie, Maho Tsubota, Mariko Maeda, Shiori Hiramoto, Fumiko Sekiguchi, Hiroyasu Ishikura, Hidenori Wake, Masahiro Nishibori, Atsufumi Kawabata
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 143 Issue 2 Pg. 112-116 (Jun 2020) ISSN: 1347-8648 [Electronic] Japan
PMID32222337 (Publication Type: Journal Article)
CopyrightCopyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Chemical References
  • Ager protein, mouse
  • Antibodies, Neutralizing
  • CXCR4 protein, mouse
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Receptor for Advanced Glycation End Products
  • Receptors, CXCR4
  • Receptors, Cytoplasmic and Nuclear
  • Thrombomodulin
  • Substance P
Topics
  • Animals
  • Antibodies, Neutralizing (therapeutic use)
  • Cystitis, Interstitial (drug therapy, etiology, genetics)
  • Disease Models, Animal
  • Female
  • HMGB1 Protein (immunology, physiology)
  • Humans
  • Male
  • Mice, Inbred Strains
  • Molecular Targeted Therapy
  • Receptor for Advanced Glycation End Products (antagonists & inhibitors)
  • Receptors, CXCR4 (antagonists & inhibitors)
  • Receptors, Cytoplasmic and Nuclear
  • Substance P (administration & dosage, adverse effects)
  • Thrombomodulin (therapeutic use)

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