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miR-181-5p attenuates neutrophilic inflammation in asthma by targeting DEK

Yilan Song1, Zhiguang Wang2, Jingzhi Jiang1

  • 1Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, Jilin, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, Jilin, PR China.

International Immunopharmacology
|September 17, 2022
PubMed

Insights

MicroRNA-181b-5p (miR-181b-5p) suppresses neutrophilic asthma by inhibiting DEK, reducing airway inflammation, and protecting mitochondria. This microRNA shows potential as a novel therapeutic target for asthma.

Area of Science:

  • Respiratory Medicine
  • Molecular Biology
  • Immunology

Background:

  • Neutrophilic asthma is characterized by airway inflammation and remodeling.
  • The role of microRNA-181b-5p (miR-181b-5p) in neutrophilic asthma is not fully understood.
  • DEK protein has been implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the regulatory role of miR-181b-5p in neutrophilic asthma.
  • To elucidate the underlying mechanisms, focusing on DEK as a potential target.
  • To evaluate miR-181b-5p as a therapeutic agent.

Main Methods:

  • Establishment of a mouse model for neutrophilic asthma.
  • In vitro studies using BEAS-2B and 16HBE cells.
  • Analysis of gene and protein expression, including DEK, MMP-2, MMP-9, and components of the Wnt/β-catenin pathway.
  • Assessment of mitochondrial function and neutrophil extracellular traps (NETs) formation.

Main Results:

  • miR-181b-5p was decreased, while DEK, MMP-2, and MMP-9 were overexpressed in neutrophilic asthma.
  • DEK was identified as a direct target of miR-181b-5p.
  • miR-181b-5p agomir administration inhibited airway inflammation and remodeling in mice.
  • miR-181b-5p suppressed the DEK/p-GSK-3βSer9/β-catenin/MMP-9 pathway and reduced NETs release.
  • DEK overexpression induced mitochondrial dysfunction, which was rescued by miR-181b-5p agomir and DKK-1.

Conclusions:

  • miR-181b-5p attenuates neutrophilic asthma by inhibiting NETs release, the DEK/Wnt/MMP-9 pathway, and mitochondrial damage.
  • miR-181b-5p demonstrates therapeutic potential for neutrophilic asthma.
Keywords:
DEKNeutrophilic asthmamiR-181b-5p

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