MiR-146a Regulates Inflammatory Infiltration by Macrophages in Polymyositis/Dermatomyositis by Targeting TRAF6 and

Yuanqin Yin1, Fei Li, Jing Shi

  • 1Cancer Institute, First Affiliated Hospital, China Medical University, Shenyang, China.

Abstract

Insights

MicroRNA-146a (miR-146a) plays a key role in polymyositis/dermatomyositis (PM/DM) by targeting TRAF6, influencing macrophage infiltration and the IL-17/ICAM-1 pathway. This finding offers new insights into PM/DM pathogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Polymyositis/dermatomyositis (PM/DM) is characterized by inflammatory macrophage infiltration.
  • The precise molecular mechanisms driving this infiltration require further elucidation.

Purpose of the Study:

  • To investigate the role of microRNA-146a (miR-146a) in macrophage infiltration in PM/DM.
  • To explore the potential targeting of TNF receptor associated factor 6 (TRAF6) by miR-146a.
  • To examine the impact on the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway.

Main Methods:

  • Analysis of muscle biopsies from PM/DM patients and healthy controls.
  • Establishment of a PM/DM rat model and macrophage isolation.
  • In vitro and in vivo treatments with miR-146a mimics/inhibitors, TRAF6 siRNAs, and pathway-specific antibodies.
  • Assessment of serum creatine phosphokinase (S-CK), CD163 expression, cell migration, and molecular targets (miR-146a, TRAF6, IL-17, ICAM-1) via ELISA, immunohistochemistry, transwell assays, RT-PCR, and western blot.

Main Results:

  • Elevated S-CK, TRAF6, IL-17, and ICAM-1 levels in PM/DM patients, reduced by conventional treatment.
  • miR-146a mimics and pathway inhibitors decreased IL-17 and ICAM-1; miR-146a inhibitors increased them.
  • TRAF6 siRNA counteracted the effects of miR-146a inhibitors, confirming TRAF6 involvement.
  • Luciferase reporter assay confirmed direct targeting of TRAF6 by miR-146a.

Conclusions:

  • MiR-146a regulates inflammatory macrophage infiltration in PM/DM.
  • This regulation occurs through targeting TRAF6 and modulating the IL-17/ICAM-1 pathway.
  • These findings highlight miR-146a as a potential therapeutic target in PM/DM.

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