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Diabetic Macrophage Exosomal miR-381-3p Inhibits Epithelial Cell Autophagy Via NR5A2

Xin Huang1, Linhesheng Wei1, Mengdi Li2

  • 1Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.

International Dental Journal
|April 29, 2024
PubMed
Abstract

Insights

Exosomes from diabetic mice macrophages disrupt autophagy in gingival cells via miR-381-3p, inhibiting NR5A2 and increasing inflammation. This reveals a key mechanism in diabetic periodontitis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Diabetes mellitus is associated with increased periodontal inflammation.
  • Autophagy plays a crucial role in maintaining cellular homeostasis and immune responses.
  • Disruption of autophagy in gingival epithelial cells (GECs) may contribute to diabetic complications.

Purpose of the Study:

  • To elucidate the mechanism by which autophagy is disrupted in GECs from diabetic individuals.
  • To investigate the role of exosomes derived from bone marrow-derived macrophages (BMDMs) in this process.

Main Methods:

  • Isolation of exosomes (Exo) from BMDMs of diabetic (db/db) and control (C57/bl) mice.
  • Co-culture of GECs with exosomes and analysis of autophagy markers (e.g., ATG7) using qRT-PCR and Western blotting.
  • Bioinformatic analysis (AnimalTFDB, TargetScan, miRDB, miRWalk) to identify transcription factors and miRNAs.
  • Functional validation using siRNA, miRNA mimics/inhibitors, and dual-luciferase assays.

Main Results:

  • Exosomes from diabetic BMDMs (ExoDM) disrupted autophagy and promoted inflammation in GECs.
  • NR5A2 was identified as a key transcription factor regulating ATG7 expression; its inhibition exacerbated inflammation.
  • miR-381-3p was identified as the primary miRNA targeting NR5A2; its inhibition restored autophagy and reduced inflammation.

Conclusions:

  • Exosomes derived from diabetic BMDMs carry miR-381-3p, which inhibits NR5A2 in GECs.
  • This inhibition disrupts autophagy, leading to increased periodontal inflammation in diabetes.
  • The miR-381-3p/NR5A2/ATG7 axis represents a critical pathway in diabetic periodontitis pathogenesis.
Keywords:
Autophagy FluxDiabetic PeriodontitisMacrophage Epithelial Cell InteractionNR5A2miR-381-3p

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