title: β-catenin as a regulator and therapeutic target for asthmatic airway remodeling.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Groningen, Groningen Research Institute for Asthma and COPD, Department of Molecular Pharmacology , A. Deusinglaan 1, 9713 AV Groningen , The Netherlands +31 50 363 8177 ; +31 50 363 6908 ; r.gosens@rug.nl.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Kumawat
authors.forename: Tim
authors.initials: T
authors.lastname: Koopmans
authors.forename: Reinoud
authors.initials: R
authors.lastname: Gosens
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018927:Anti-Asthmatic Agents; D051176:beta Catenin
keywords: WNT; airway smooth muscle; asthma; catenin