Abstract
Exposure to PM2.5 has become one of the most important factors affecting public health in the world. Both clinical and research studies have suggested that PM2.5 inhalation is associated with impaired lung function. In this study, material characterization identified the existence of nanoscale particulate matter (NPM) in airborne PM2.5 samples. When coming into contact with protein-rich fluids, the NPM becomes covered by a protein layer that forms a “protein corona”. Based on a 3D organotypic cell culture, the protein corona was shown to mitigate NPM cytotoxicity and further stimulate the proliferation of human lung fibroblasts (HLFs). ROS-activated alpha-smooth muscle actin (α-SMA) is considered to be one of the proliferation pathways. In this research, 3D cell cultures exhibited more tissue-like properties compared with the growth in 2D models. Animal models have been widely used in toxicological research. However, species differences make it impossible to directly translate discoveries from animals to humans. In this research, the 3D HLF model could partly simulate the biological responses of NPM-protein corona-induced aberrant HLF proliferation in the human lung. Our 3D cellular results provide auxiliary support for an animal model in research on PM2.5-induced impaired lung function, particularly in lung fibrosis.
Highlights
Exposure to PM2.5 has become one of the most important factors affecting public health in the world
The results demonstrated that the nanoscale particulate matter (NPM)-protein corona stimulated human lung fibroblasts (HLFs) to express α-SMA. α-SMA expression was positively correlated with the NPM exposure concentration (Fig. 8A)
Our results (SEM and FTIR) demonstrated that NPM particles were surrounded by a protein cloud to form a “protein corona”
Summary
Exposure to PM2.5 has become one of the most important factors affecting public health in the world Both clinical and research studies have suggested that PM2.5 inhalation is associated with impaired lung function. The 3D HLF model could partly simulate the biological responses of NPM-protein corona-induced aberrant HLF proliferation in the human lung. The human organotypic 3D cell model provides auxiliary support for animal models in toxicology research and could partly simulate the physiological response of humans[15]. Fibrin scaffolds, produced by polymerizing the protein fibrinogen obtained from plasma, have been widely investigated for a variety of tissue engineering applications[20,21] These include the study of fibroblast activation and proliferation based on fibroblast-fibrin matrix culture models[22,23]. It is believed that fibrin matrix 3D culture models will be a useful platform to investigate PM2.5 involvement in pulmonary dysfunction
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