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

作者：Jingjing Xia, Zhuo Xiong, Jiaxuan Guo, Yongan Wang, Yuan Luo, Yangyang Sun, Zhongwei Guo, Bingchuan Lu, Ting Zhang, Wei Sun · 发表于：Biofabrication · 年份：2022 · DOI：10.1088/1758-5090/ac999e · 被引用次数：24 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Paraquat toxicity studies and treatments

Abstract 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 lung 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 µ M). 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 ce...