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Study of paraquat-induced pulmonary fibrosis using biomimetic micro-lung chips
Journal article   Peer reviewed

Study of paraquat-induced pulmonary fibrosis using biomimetic micro-lung chips

Jingjing Xia, Zhuo Xiong, Jiaxuan Guo, Yongan Wang, Yuan Luo, Yangyang Sun, Zhongwei Guo, Bingchuan Lu, Ting Zhang and Wei Sun
Biofabrication, v 15(1), 014104
01 Jan 2023
PMID: 36223759
url
https://doi.org/10.1088/1758-5090/ac999eView
Published, Version of Record (VoR) Open

Abstract

A549 Cells Animals Humans Lung - metabolism Paraquat - adverse effects Paraquat - metabolism Pulmonary Fibrosis - chemically induced Pulmonary Fibrosis - pathology Rats Vimentin - metabolism Biomimetics
Paraquat (PQ) poisoning induces pulmonary fibrosis in vivo. The pathogenesis of pulmonary fibrosis is complex, which has prevented the development of specific treatments. Pulmonary fibrosis shows several characteristics including epithelial-mesenchymal transition (EMT), fibroblast activation, and extracellular matrix (ECM) deposition. To investigate pulmonary fibrosis, we designed a biomimetic multichannel micro-lung chip to imitate the in vivo interface between the lu epithelium and the lung interstitium. In our model, A549 (lung epithelial cells) and MRC-5 (fetal lung fibroblasts) cells were used to test the efficacy of our chip-based model. Rat tail type I collagen and hyaluronic acid were used to simulate ECM and to provide a 3D microenvironment. The micro-lung chips were cultured with PQ (0, 75, 150, 300, and 400 µM). The viability of A549 and MRC-5 cells significantly decreased with increasing PQ concentrations. There were significant changes in surfactant proteins C (SP-C), alpha smooth muscle actin protein (α-SMA), and vimentin protein levels during PQ-induced pulmonary fibrosis. SP-C levels were decreased in A549 cells, while those of α-SMA and vimentin were increased in A549 cells and MRC-5 cells treated with PQ in the micro-lung chip. We also designed a reference model without interaction between the lung epithelial cells and fibroblasts. Compared to the non-contact model, co-culturing A549 and MRC-5 cells in chips induced more severe EMT in A549 cells after treatment with 75 µM PQ and together defended against PQ-induced damage. Thus, our novel co-culture micro-lung chip that models the lung epithelium and interstitium may provide a new approach for studying lung fibrosis and will facilitate drug development.

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16 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Engineering, Biomedical
Materials Science, Biomaterials
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