An Air–Liquid Interface Organ-Level Lung Microfluidics Platform for Analysis on Molecular Mechanisms of Cytotoxicity Induced by Cancer-Causing Fine Particles

• DOI: 10.1021/acssensors.8b01672
• Publication Date: 2019-03-07T14:23:22Z
• Authors: Lulu Zheng; Heng Dong; Wang Zhao; Xinlian Zhang; Xiaoxiao Duan; Hao Zhang; Sixiu Liu; Guodong Sui
• Keywords: Biological pathway

Fine particulate matter less than 2.5 μm in diameter (PM2.5) is regarded as a carcinogenic factor, but the mechanism has been left unexplored. Our goal was to reveal at gene and protein level under inhalational air-liquid interface (ALI) condition. Herein, we developed an ALI organ-level lung microfluidic platform (ALI-OLMP) carrying epithelial cell line BEAS-2B human pulmonary microvascular endothelial cells (HPMEC); viability above 98% within 14 days on this system, which used mimic practical alveolar microenvironment for multiomics analysis, identify global expression after exposure PM2.5 Shanghai, China from 2014 2015. The combined RNA-Seq iTRAQ analysis indicated that unique set 2532 genes 10 μg/cm2 of PM2.5, there were also least 25 identical activated signal transduction cascades including bladder cancer, transcriptional dysregulation TP53 (p53) signaling pathway, Jak-STAT PI3K-Akt could lead blocking differentiation, proliferation survival, sustained angiogenesis. images obtained by transmission electron microscopy (TEM) showed particles enter mitochondria, even get into nucleus. Pearson's correlation coefficient test elucidated inorganics (EC), organics (OC, PAHs, alkane), metals (Cr, Mn, Sb) significantly correlated dysregulated oncoproteins (VEGF, IL6, MDM2, AKT1, STAT, P53). findings may some extent explain molecular carcinogenicity caused fine-particle exposure.