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DCLK1 mediates airway epithelial barrier disruption through NF-κB activation in severe asthma

Wun-Hao Cheng1,2,3,4, Mei-May Neoh1,4, Kuan-Yuan Chen3,5

  • 1School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan.

Molecular Medicine (Cambridge, Mass.)
|May 29, 2026
PubMed
Abstract

Insights

Doublecortin-like kinase 1 (DCLK1) promotes airway epithelial barrier dysfunction in severe asthma by activating NF-κB signaling. Targeting DCLK1 may restore epithelial integrity and offer a new therapeutic strategy for severe asthma.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Immunology

Background:

  • Severe asthma involves epithelial barrier defects, airway remodeling, and inflammation.
  • Doublecortin-like kinase 1 (DCLK1), a cancer stem cell marker, is implicated in NF-κB inflammatory pathways.
  • The specific role of DCLK1 in TGF-β-induced epithelial barrier disruption in severe asthma is not well understood.

Purpose of the Study:

  • To investigate the role of DCLK1 in TGF-β-induced epithelial barrier dysfunction in severe asthma.
  • To explore DCLK1's mechanism in mediating epithelial-mesenchymal transition (EMT) and NF-κB activation.
  • To evaluate DCLK1 as a potential therapeutic target for severe asthma.

Main Methods:

  • Examined DCLK1 and junctional protein expression in severe asthma patient biopsies and air-liquid interface cultures.
  • Utilized in vitro (BEAS-2B cells) and in vivo (murine asthma models) approaches to study DCLK1 function.
  • Employed global DCLK1 knockout mice to assess its impact on epithelial integrity, airway remodeling, and inflammation.

Main Results:

  • DCLK1 expression is elevated in bronchial epithelial cells of severe asthma patients.
  • DCLK1 silencing restored epithelial barrier function, reversed TGF-β-induced EMT, and reduced fibronectin/N-cadherin.
  • DCLK1 knockout mice showed improved lung function and reduced airway inflammation in response to allergens.

Conclusions:

  • DCLK1 drives airway epithelial barrier dysfunction in severe asthma via NF-κB activation.
  • Targeting DCLK1 presents a promising therapeutic avenue for restoring epithelial integrity in severe asthma.
  • Further research into DCLK1 inhibition could lead to novel treatments for severe asthma.
Keywords:
Doublecortin-like kinase 1EMTNF-κBOVA/HDMairway fibrosisasthma

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