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

Expert Opin Ther Targets. 2014 Sep;18(9):1023-34. doi: 10.1517/14728222.2014.934813. Epub 2014 Jul 8.

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 β-catenin in remodeling asthmatic airways. The WNT/β-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 β-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 β-catenin signaling activation and its mechanistic role in asthmatic airway remodeling. Further, we discuss the possibilities of therapeutic targeting of β-catenin.

Expert opinion: The aberrant activation of β-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 β-catenin signaling directly.

Keywords: WNT; airway smooth muscle; asthma; catenin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Airway Remodeling / physiology*
  • Animals
  • Anti-Asthmatic Agents / pharmacology
  • Asthma / drug therapy
  • Asthma / physiopathology*
  • Bronchoconstriction / physiology
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Extracellular Matrix / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Wnt Signaling Pathway / physiology
  • beta Catenin / metabolism*

Substances

  • Anti-Asthmatic Agents
  • beta Catenin