Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Acta Cir Bras. 2023 Dec 1:38:e385123. doi: 10.1590/acb385123. eCollection 2023.

Abstract

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism.

Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment.

Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-β/SMAD pathways.

Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

MeSH terms

  • Animals
  • Cystitis* / drug therapy
  • Cystitis, Interstitial* / drug therapy
  • Cystitis, Interstitial* / metabolism
  • Cystitis, Interstitial* / pathology
  • Emodin* / pharmacology
  • Emodin* / therapeutic use
  • Fibrosis
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Mice

Substances

  • Emodin