PM2.5, Fine Particulate Matter: A Novel Player in the Epithelial-Mesenchymal Transition?

Abstract

Epithelial-mesenchymal transition (EMT) refers to the conversion of epithelial cells to mesenchymal phenotype, which endows the epithelial cells with enhanced migration, invasion, and extracellular matrix production abilities. These characteristics link EMT with the pathogenesis of organ fibrosis and cancer progression. Recent studies have preliminarily established that fine particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) is correlated with EMT initiation. In this pathological process, PM2.5 particles, excessive reactive oxygen species (ROS) derived from PM2.5, and certain components in PM2.5, such as ions and polyaromatic hydrocarbons (PAHs), have been implicated as potential EMT mediators that are linked to the activation of transforming growth factor β (TGF-β)/SMADs, NF-κB, growth factor (GF)/extracellular signal-regulated protein kinase (ERK), GF/phosphatidylinositol 3-kinase (PI3K)/Akt, wingless/integrated (Wnt)/β-catenin, Notch, Hedgehog, high mobility group box B1 (HMGB1)-receptor for advanced glycation end-products (RAGE), and aryl hydrocarbon receptor (AHR) signaling cascades and to cytoskeleton rearrangement. These pathways directly and indirectly transduce pro-EMT signals that regulate EMT-related gene expression in epithelial cells, finally inducing the characteristic alterations in morphology and functions of epithelia. In addition, novel associations between autophagy, ATP citrate lyase (ACLY), and exosomes with PM2.5-induced EMT have also been summarized. However, some debates and paradoxes remain to be consolidated. This review discusses the potential molecular mechanisms underlying PM2.5-induced EMT, which might account for the latent role of PM2.5 in cancer progression and fibrogenesis.

Small airway remodeling in diabetic and smoking chronic obstructive pulmonary disease patients

“…As the first line of protection for the airways and lungs, the epithelium is an essential barrier against outer irritants [13,14]. However, when AECs are overexposed to irritants such as CS and other environmental factors, they can undergo EMT, characterized by the loss of polarity, reduced epithelial marker expression, loss of tight junctions, and increased mesenchymal characteristics such as motility, depolarized cytoskeletal arrangements, vimentin and alpha smooth muscle actin overexpression and so on [15][16][17]. Various studies by Sohal, Soltani, Mahmood and others have demonstrated that small airway dysfunction is associated with EMT [18][19][20][21][22][23][24].…”

Ma Xing Shi Gan Decoction Protects against PM2.5‐Induced Lung Injury through Suppression of Epithelial‐to‐Mesenchymal Transition (EMT) and Epithelial Barrier Disruption

“…Among these cytokines, TGF-β, an efficient profibrotic cytokine, is one of the most essential factors initiating the phenotypic transition of fibroblasts to myofibroblasts, which mediates the EMT progress [61][62][63]. e critical role of TGF-β-mediating Smad (mainly Smad3) signaling has been demonstrated in EMT associated with PM2.5 stimulation, bleomycin challenge, and tumour progression/development [18,19,[64][65][66][67][68][69]. TGFβ signals are transduced through transmembrane serine/ threonine kinase receptors.…”

The Inducible Role of Ambient Particulate Matter in Cancer Progression via Oxidative Stress-Mediated Reactive Oxygen Species Pathways: A Recent Perception

“…There was a report that PM2.5 might induce c-Jun-dependent AP-1 activation through oxidative stress-mediated activation of MAPKs [64]. Ultimately, these signaling pathways together influence the tumor microenvironment, which is important for tumor behavior, as well as the epithelial-mesenchymal transition (EMT), which promotes tumor cell migration and invasion [78,79].…”