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

Zihan Xu,Wenjun Ding,Xiaobei Deng

doi:10.3389/fphys.2019.01404

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.

Highlights

Air pollution, especially that of developing countries, has become increasingly severe with the process of industrialization
After 5 weeks of PM2.5 exposure, hypomethylated CpG islands (CpGs) in the genome of bronchial epithelial cells were significantly enriched in genes associated with GTPase activity, extracellular matrix organization, and growth factors (GFs) stimuli, whereas hypermethylated CpGs were clustered in genes responsible for cell adhesion and ion transportation (Hesselbach et al, 2017)
On the basis of studies investigating PM2.5 toxicology, in this review, we describe that PM2.5 might induce Epithelial-mesenchymal transition (EMT) by intermediary reactive oxygen species (ROS), which induce the secretion of transforming growth factor β (TGF-β), IL-6, IL-8, and TNF-α, as well as the activation of the SMADs, NF-κB, The Janus kinase (JAK)/Signal transducers and activators of transcription-3 (STAT3), extracellular signal-regulated protein kinase (ERK), Akt, and Rho GTPasedependent cascades

Summary

Introduction

Especially that of developing countries, has become increasingly severe with the process of industrialization. Transitional metals, soluble salts, organic/elemental carbon, and microbes that adhere to PM2.5 particles contribute to the toxic effects of PM2.5 including inflammation, DNA damage, mutations, reactive oxygen species (ROS) accumulation, and mitochondria dysfunction. All these abnormal intracellular events are highly correlated with the pathogenesis and progression of a series of human diseases (Ghio et al, 2012; Valavanidis et al, 2013; Feng et al, 2016; Qi et al, 2019). Maternal exposure to PM2.5 is linked to an increased risk of airway disease development in offspring (Saha et al, 2018; Sanyal et al, 2018)

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