Novel Therapeutic Strategies for Fibrotic Lung Disease: A Review with a Focus on Epithelial-Mesenchymal Transition
Satoshi Noguchi, Yasuhiro Yamauchi and Hajime TakizawaAffiliation:
Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
AbstractAirway and pulmonary fibrosis is a pathological condition associated with chronic airway inflammation. Fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The traditional paradigm of fibrogenesis is based on the activation of local stromal cells including fibroblasts and their conversion into myofibroblasts. However, it has become apparent that several airway structural cells, including epithelial cells, endothelial cells, and pericytes, contribute to lung fibrosis through a process of molecular reprogramming. Recent studies have shown the important role of epithelial-mesenchymal transition (EMT) in airway diseases and animal models of fibrosis, suggesting that targeting EMT may be a promising strategy against fibrotic lung disease. In this article, we review the latest advances on the evidence for EMT in airway diseases, and discuss the underlying mechanisms of EMT and the roles of inflammatory mediators. We also describe recent patents that could develop into novel therapeutics.
Chronic inflammatory airway diseases, EMT, fibrosis, myofibroblast, TGF-β, TNF-α.
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