β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Kuldeep Kumawat, Tim Koopmans, Reinoud Gosens*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

36 Citations (Scopus)

Abstract

Introduction: Pathological alteration in the airway structure, termed as airway remodeling, is a hallmark feature of individuals with asthma and has been described to negatively impact lung function in asthmatics. Recent studies have raised considerable interest in the regulatory role of beta-catenin in remodeling asthmatic airways. The WNT/beta-catenin signaling pathway is the key to normal lung development and tightly coordinates the maintenance of tissue homeostasis under steady-state conditions. Several studies indicate the crucial role of beta-catenin signaling in airway remodeling in asthma and suggest that this pathway may be activated by both the growth factors and mechanical stimuli such as bronchoconstriction.

Areas covered: In this review, we discuss recent literature regarding the mechanisms of beta-catenin signaling activation and its mechanistic role in asthmatic airway remodeling. Further, we discuss the possibilities of therapeutic targeting of beta-catenin.

Expert opinion: The aberrant activation of beta-catenin signaling by both WNT-dependent and -independent mechanisms in asthmatic airways plays a key role in remodeling the airways, including cell proliferation, differentiation, tissue repair and extracellular matrix production. These findings are interesting from both a mechanistic and therapeutic perspective, as several drug classes have now been described that target beta-catenin signaling directly.

Original languageEnglish
Pages (from-to)1023-1034
Number of pages12
JournalEXPERT OPINION ON THERAPEUTIC TARGETS
Volume18
Issue number9
DOIs
Publication statusPublished - Sep-2014

Keywords

  • airway smooth muscle
  • asthma
  • catenin
  • WNT
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • FOCAL ADHESION KINASE
  • SMOOTH-MUSCLE-CELLS
  • EXTRACELLULAR-MATRIX PRODUCTION
  • PULMONARY-FIBROSIS
  • PRESCHOOL WHEEZERS
  • MATERNAL SMOKING
  • LUNG-CANCER
  • PROTEIN CBP
  • MOUSE LUNG

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