期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 18, 期 9, 页码 1023-1034出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.934813
关键词
airway smooth muscle; asthma; catenin; WNT
资金
- Vidi grant from the Dutch Organization for Scientific Research (NWO) [016.126.307]
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.
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