Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

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.

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

“…EMT is a process during which epithelial cells lose their epithelial cell marker such as E-cadherin and acquire mesenchymal characteristics as α-SMA and Collagen I. EMT has been con rmed to occur in several pathological processes, including tumor invasion [29] , acute renal injury [30] , and pulmonary brosis [31,32] . Here, we demonstrated that the EMT also developed in the lungs after LPS exposure, which was coincident with increased expression of EZH2 and H3K27me3; EZH2 inhibition signi cantly restored epithelial cellular markers and inhibited bro-proliferation.…”

“…The mechanism of 3-DZNeP-eliciated different effect in these studies remains unclear, but may be related to the use of different models. Nevertheless, apart from the Smad pathway, TGF-β1 induced EMT and brosis is also associated with activation of other signaling pathways, such as as MEK/ERK, PI3K/Akt, and Wnt/βcatenin [31] . Further investigations are needed to explore the relationships between EZH2 and Smadindependent pathways.…”

Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

“…as N-cadherin and α-SMA [49]. Although the exact origin of activated myofibroblasts remains uncertain, recent studies showed that the EMT process is essential in the pathogenesis of lung fibrosis [50,51]. In the present work, EMT and lung fibrosis were observed in diabetic rats, and this could be reversed, at least in part, by MSCs via enhancing autophagy and suppressing inflammation, oxidative stress, apoptosis, and ER stress, suggesting that MSCs play protective effects against diabetic lung fibrosis.…”

Increased FOXL2 Expression Alters Uterine Structures and Functions

“…The severely retarded adenogenesis in the FOXL2 OE uterus might be one of the major players in the failed decidualization. Besides, endometrial decidualization is promoted by mesenchymal-epithelial transition (MET) [75], while fibrosis is positively correlated with epithelial-mesenchymaltransition (EMT) [76]. Therefore, the exaggerated fibrosis observed in the FOXL2 OE uterine stroma might also blunt the decidualization through inhibiting the MET process.…”