Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse

Menglu Chen1, Lei Gao2, Pan Chen2

  • 1Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China; Department of Clinical Laboratory, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.

Insights

Serotonin (5-HT) worsens dextran sulfate sodium-induced colitis by increasing matrix metalloproteinases (MMPs) in the colon. This study shows 5-HT upregulates MMP-3 and MMP-9, contributing to intestinal inflammation.

Area of Science:

  • Gastroenterology and Hepatology
  • Immunology
  • Molecular Biology

Background:

  • Serotonin (5-HT) is implicated in inflammatory bowel disease (IBD) pathogenesis.
  • Matrix metalloproteinases (MMPs) are key mediators of intestinal inflammation.
  • 5-HT is known to enhance dextran sulfate sodium- (DSS-) induced colitis.

Purpose of the Study:

  • To investigate if 5-HT induces MMP expression in the mouse colon.
  • To determine the role of 5-HT-induced MMPs in exacerbating DSS-induced colitis.

Main Methods:

  • Mice were treated with 5-HT and/or DSS via enema.
  • Colitis severity was assessed.
  • Messenger RNA (mRNA) levels of MMPs and tissue inhibitors of MMPs (TIMPs) were quantified using real-time quantitative RT-PCR.
  • Protein levels of MMP-3 and MMP-9 were analyzed via immunohistochemistry (IHC).

Main Results:

  • 5-HT exacerbated DSS-induced colitis.
  • Low-dose 5-HT increased both MMP-3 and MMP-9 mRNA; high-dose 5-HT increased MMP-3 mRNA in mouse colon.
  • 5-HT treatment elevated MMP-3 and MMP-9 protein levels in the mouse colon.
  • MMP-2, TIMP-1, and TIMP-2 mRNA levels were elevated in inflamed colons.
  • In vitro, 5-HT induced MMP-3 and MMP-9 mRNA in Caco-2 cells and neutrophils, respectively.

Conclusions:

  • 5-HT induces the expression of MMP-3 and MMP-9 in the mouse colon.
  • Elevated MMP levels mediated by 5-HT may contribute to the severity of DSS-induced colitis.
  • These findings highlight a potential therapeutic target for IBD.

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