microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical

Shao Lina1, Qiu Lihong1, Yang Di1

  • 1Department of Endodontics, School of Stomatology, China Medical University, China.

Insights

MicroRNA-146a (miR-146a) and Hey2 regulate inflammation in chronic apical periodontitis (CAP). They form a feedback loop, impacting inflammatory responses in CAP by targeting key inflammatory molecules.

Area of Science:

  • Oral Biology
  • Immunology
  • Molecular Biology

Background:

  • Chronic apical periodontitis (CAP) involves inflammation of the dental pulp and root canal system.
  • Porphyromonas endodontalis lipopolysaccharide (P. endodontalis LPS) is a key inducer of inflammation in CAP.
  • MicroRNA-146a (miR-146a) is a critical regulator of inflammatory responses, and Hey2 is involved in pulp repair.

Purpose of the Study:

  • To investigate the role of miR-146a targeting Hey2 in CAP.
  • To elucidate the underlying molecular mechanisms of miR-146a and Hey2 in CAP-induced inflammation.

Main Methods:

  • Analysis of miR-146a and Hey2 expression in CAP patients and healthy controls.
  • In vitro stimulation of MC3T3-E1 cells with P. endodontalis LPS.
  • Luciferase reporter assay to confirm Hey2 as a target gene of miR-146a.
  • Assessment of inflammatory cytokine expression (IL-6, IL-1β, TNF-α).

Main Results:

  • miR-146a and Hey2 expression were significantly elevated in CAP patients.
  • P. endodontalis LPS increased the expression of miR-146a, Hey2, IL-6, IL-1β, and TNF-α in vitro.
  • miR-146a negatively regulated inflammatory cytokine expression, and Hey2 was validated as a miR-146a target.
  • Hey2 also negatively regulated inflammatory markers and was recruited to the IL-6 promoter by P. endodontalis LPS.

Conclusions:

  • miR-146a and Hey2 form a mutual negative feedback loop that regulates inflammatory responses in CAP.
  • This study reveals a novel mechanism involving miR-146a and Hey2 in the pathogenesis of chronic apical periodontitis.

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