Abstract
Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a specific form of interstitial pneumonia that leads to progressive, irreversible scarring of the lung and death due to respiratory failure within five years in approximately 50% of the patients [1]
epithelial–mesenchymal transition (EMT) is regulated by multiple extracellular ligands, such as transforming growth factor-beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), interleukin-1 (IL-1), connective tissue growth factor (CTGF), insulin-like growth factor-2 (IGF-2), nuclear factor-kB (NF-kB) and Wnt, that initiate intracellular signaling cascades after binding to surface receptors [18,20]
Convincing evidence has recently been provided that EMT contributes to the early development of interstitial fibrosis via paracrine signaling directed from the alveolar epithelium to underlying fibroblasts [48]
Summary
Idiopathic pulmonary fibrosis (IPF) is a specific form of interstitial pneumonia that leads to progressive, irreversible scarring of the lung and death due to respiratory failure within five years in approximately 50% of the patients [1]. Stem cell exhaustion in IPF lung seems to drive abnormal repair and failure of alveolar regeneration with aberrant expression of Wnt/β-catenin and other developmental pathways [13,14] (Figure 1) This creates a profibrotic environment in which collagen-producing fibroblasts and myofibroblasts accumulate through different mechanisms such as proliferation and differentiation of resident lung fibroblasts, transition of bone-marrow derived fibrocytes or other circulating progenitors to fibroblasts and epithelial-to-mesenchymal transition (EMT) [15,16]. Hedgehog and transforming growth factor-beta (TGF-β)) due to the inability of the alveolar epithelium to regenerate This creates a pro-fibrotic environment in which loss of epithelial phenotype, acquisition of mesenchymal phenotype, fibroblasts activation and collagen production take place.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
