Emt and interstitial lung disease a mysterious relationship

EMT and interstitial lung disease: a mysterious relationship.

EMT. and. interstitial. lung. disease: a. mysteri0us. relationship. By a News Reporter-Staff News Editor at Respiratory Therapeutics Week — Researchers detail. Curr Opin Pulm Med. Sep;18(5) doi: /MCP. 0be EMT and interstitial lung disease: a mysterious relationship. Kage H(1). Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology, and is the most common subtype of idiopathic interstitial pneumonia. and its relationship with lung cancer, with an emphasis on TGF-β signaling. First . TGF-β is also known to strongly elicit EMT, a phenotypic change whereby.

AECs contain two different types, I and II, and less is known about the relationship between the two major types.

EMT and Interstitial Lung Disease: A Mysterious Relationship

AEC type II is more important in alveolar repair and regeneration based on animal studies in bleomycin-induced lung injury. In addition, AECs may activate a progenitor population for epithelial repair and regeneration during alveolar injury [ 11 ]. Certainly, there are more published articles using cell lineage fate-mapping techniques or fluorescent markers to support EMT versus against it [ 12 ]. The main reason to see the contrary evidences may result from the time point to trace the cell lineage.

Expression of the fluorescent marker at a later time point will cause loss of some subpopulation of epithelial cells which may undergo EMT. Intra-trachelbleomycin was administered to these mice and to littermate control mice lacking one of the transgenes.

Mice with lung epithelial-specific deletion of col1a1 demonstrate significantly reduced accumulation of total collagen Yang et al.

EMT and interstitial lung disease: a mysterious relationship.

This is strong evidence to support EMT-derived contribution of collagen I in the extracellular matrix. Another principal role for EMT in repair is promotion of fibrosis through epithelial-mesenchymal crosstalk signaling pathways. The crosstalk may be presented not only in secretion of pro-fibrotic factors, but also in production of cytokines to recruit fibrocytes into the lung.

Expression of a mutant surfactant protein C LQ induced ER stress in mice which showed exaggerated lung fibrosis and increased apoptosis of AECs, implying that a dysfunctional AEC phenotype will promote fibrotic remodeling [ 14 ]. Conclusions and Challenge IPF is a highly heterogeneous and lethal progressive disease due to the excessive deposition of extracellular matrix within the lung interstitial area. Although what exactly can trigger IPF is still unknown, a common acceptable concept is the initial dysfunctional repair and remodeling following AECs injury.

During epithelial cell dysfunction, EMT contributes significantly to collagen I secretion which may act to recruit or activate local lung fibroblasts. Other mechanism includes epigenetic regulation of AECs or fibroblasts injury which has not been discussed here. Future challenge mainly comes from further understanding of the signaling pathways that control several key checkpoints during the fibrogenesis including initial epithelial injury, EMT, myofibroblast activation, matrix metalloproteinase secretion, etc.

Lineage tracing yielded conflicting results, with two recent studies supporting and one opposing a role for EMT in lung fibrosis. Summary Advances have been made in elucidating causes and mechanisms of EMT, potentially leading to new treatment options, although contributions of EMT to lung fibrosis in vivo remain controversial. In addition to EMT providing a direct source of myo fibroblasts, expression of mesenchymal markers may reflect epithelial injury, in which case inhibition of EMT might be deleterious.

EMT-derived cells may also contribute to aberrant epithelial-mesenchymal crosstalk that promotes fibrogenesis. The cause of ILD is sometimes known e.

The Pathogenesis of Idiopathic Pulmonary Fibrosis Focusing on Epithelial Cells

When the cause is unknown, it is labeled as idiopathic and further classified into the currently recognized single disease entities [ 1 ]. Research on pathogenesis has been conducted mostly in the context of the most frequent of idiopathic ILD, idiopathic pulmonary fibrosis IPF. In the currently accepted paradigm, a major factor in IPF pathogenesis is thought to be recurrent alveolar epithelial cell AEC injury [ 23 ].

Initial injury leads to aberrant activation of AEC, creating a profibrotic environment with accumulation of collagen-producing fibroblasts and myofibroblasts. To date, myo fibroblasts have been suggested to accumulate via three mechanisms: The significance and relative contribution of each pathway to fibrosis have not been definitively established, hampering development of novel therapies.

We first review the latest advances on causes and underlying mechanisms of EMT and then focus on the ongoing controversy of whether and how EMT contributes to lung fibrosis and whether inhibition of EMT would be of benefit therapeutically. Potential causes of EMT Historically, disruption of cell contacts, hypoxia and inflammation have been proposed as potential triggers of EMT [ 5 ].

EMT and interstitial lung disease: a mysterious relationship. - Semantic Scholar

In recent years, progress has been made in understanding the relationship between endoplasmic reticulum ER stress and IPF [ 6 ]. The ER is an organelle where secreted and membrane proteins fold and mature, and ER stress refers to activation of signaling pathways in response to relative insufficiency in protein folding capacity [ 7 ].

In the lung, mutations in genes encoding surfactant proteins SP-A2 and SP-C are associated with interstitial lung diseases [ 8 — 11 ], and ER stress due to mutant protein accumulation has been the proposed underlying mechanism leading to apoptosis and fibrosis [ 1213 ].

In addition, Zhong et al. Two papers have reported on interactions between epithelial cells and extracellular matrix, which in turn lead to EMT.