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

Ye-Fang Wang,Jian-Ping Zhu,Yu-Xiang Fei,Wei-Rong Fang,Bo-Wen Wang,Qi-Yang Yin,Bo Zhao,Yun-Man Li,Guang-Hui Ren

doi:10.1155/2020/7176589

Abstract

This research was designed to explore the effect of Ma Xing Shi Gan decoction (MXD) in alleviating particulate matter less than 2.5 μm in diameter (PM2.5) induced lung injury from the perspective of epithelial barrier protection and inhibition of epithelial-to-mesenchymal transition (EMT). Rats were exposed to PM2.5 to establish a lung injury model in vivo, and a PM2.5-stimulated primary cultured type II alveolar epithelial cell model was introduced in vitro. Our results indicated that MXD alleviated the weight loss and pathologic changes and improved the epithelial barrier dysfunction. MXD also significantly inhibited the TGF-β/Smad3 pathway, increased the level of ZO-1 and claudin-5, and reversed the EMT process. Notably, the protection of MXD was abolished by TGF-β in vitro. Our results indicated that MXD has a protection against PM2.5-induced lung injury. The proposed mechanism is reversing PM2.5-induced EMT through inhibiting TGF-β/Smad3 pathway and then upregulating the expression of tight-junction proteins.

Highlights

Particulate matter (PM) is a major component of air contamination. ere is a positive correlation between PM concentrations and the morbidity rates, which was evidenced by epidemiologic studies [1,2,3,4].PMs less than 2.5 μm in diameter (PM2.5) are likely to be deposited deep in the lungs [5]
As a critical line of defence, the airway epithelium regularly forms a barrier against invasion of inhaled environmental agents including but not limited to pollutants and pathogens [13]. e epithelial barrier function largely depends on the tight junction surrounding epithelial cells, which forms ordered belt-like structure and regulate the flow of foreign substances [14]
Ma Xing Shi Gan decoction (MXD) Improved PM2.5-Induced Lung Histopathological Changes. e lung tissue structures and morphological changes were evaluated with hematoxylin and eosin (H&E) staining 2 h after the last drug administration

Summary

Introduction

Particulate matter (PM) is a major component of air contamination. ere is a positive correlation between PM concentrations and the morbidity (and mortality) rates, which was evidenced by epidemiologic studies [1,2,3,4].PMs less than 2.5 μm in diameter (PM2.5) are likely to be deposited deep in the lungs [5]. Recent studies have testified that PMs contribute to airway hyperactivity, macrophage excessive activation, and epithelial damage [6,7,8,9,10]. As a critical line of defence, the airway epithelium regularly forms a barrier against invasion of inhaled environmental agents including but not limited to pollutants and pathogens [13]. E epithelial barrier function largely depends on the tight junction surrounding epithelial cells, which forms ordered belt-like structure and regulate the flow of foreign substances [14]. In response to epithelial challenge (including particulate, radiation, drug stimulation, bacterial/ virus infection), epithelial cells will undergo epithelial-tomesenchymal transition (EMT), contributing to the resultant fibrosis [15, 16]. A representative event during EMT process is the decomposition of tight junctions, which is evidenced by the redistribution of barrier-related proteins including zonula

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Conclusion