Journal article
Study of paraquat-induced pulmonary fibrosis using biomimetic micro-lung chips
Biofabrication, v 15(1), 014104
01 Jan 2023
PMID: 36223759
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 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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Details
- Title
- Study of paraquat-induced pulmonary fibrosis using biomimetic micro-lung chips
- Creators
- Jingjing Xia - Tsinghua UniversityZhuo Xiong - Tsinghua UniversityJiaxuan Guo - Tsinghua UniversityYongan Wang - Institute of PharmacologyYuan Luo - Institute of PharmacologyYangyang Sun - Institute of PharmacologyZhongwei Guo - School of Mechanics and Safety Engineering, Zhengzhou University, Zhengzhou 450001, People's Republic of ChinaBingchuan Lu - 'Biomanufacturing and Engineering Living Systems' Innovation International Talents Base (111 Base), Beijing 100084, People's Republic of ChinaTing Zhang - Tsinghua UniversityWei Sun - Drexel University, Mechanical Engineering and Mechanics
- Publication Details
- Biofabrication, v 15(1), 014104
- Publisher
- IOP Publishing
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:000880828000001
- Scopus ID
- 2-s2.0-85141890485
- Other Identifier
- 991021860722904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials