Protective role of TRPM7 knockdown in ulcerative colitis via blocking NLRP3 inflammasome-mediated pyroptosis

Jinzhen Peng1, Shuai Tang1, Lifang Huang2

  • 1Department of gastroenterology, Shaoguan First People's Hospital, Shaoguan 512000, PR China.

PubMed

Insights

Targeting TRPM7 (Transient Receptor Potential Melastatin 7) shows therapeutic potential for ulcerative colitis (UC). Reducing TRPM7 alleviates inflammation and gut barrier damage by inhibiting NLRP3-dependent pyroptosis.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Transient receptor potential melastatin 7 (TRPM7) exhibits ion channel and kinase functions, making it a potential target for immunomodulation.
  • Ulcerative colitis (UC) is a chronic inflammatory bowel disease with complex underlying mechanisms.

Purpose of the Study:

  • To investigate the role of TRPM7 in the pathogenesis of ulcerative colitis (UC).
  • To elucidate the molecular mechanisms by which TRPM7 influences UC progression.

Main Methods:

  • Established in vivo murine and in vitro cell models of UC using DSS stimulation.
  • Assessed TRPM7 expression via RT-qPCR and Western blotting.
  • Evaluated colonic damage, inflammation, oxidative stress, and intestinal barrier function using various assays (H&E, DAI, MPO, ELISA, FITC-dextran flux, TEER).
  • Investigated NLRP3-dependent pyroptosis using immunofluorescence and Western blotting.

Main Results:

  • TRPM7 depletion significantly reduced inflammation, oxidative damage, and intestinal barrier dysfunction in both in vitro and in vivo UC models.
  • Silencing TRPM7 suppressed NLRP3 inflammasome-mediated pyroptosis.
  • Administration of an NLRP3 agonist partially reversed the protective effects of TRPM7 silencing.

Conclusions:

  • TRPM7 plays a crucial role in UC development.
  • TRPM7 deletion demonstrates therapeutic potential for UC by inhibiting NLRP3-dependent pyroptosis.
  • Targeting TRPM7 may offer a novel therapeutic strategy for managing ulcerative colitis.

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