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Updated: Aug 8, 2026
An Air-liquid Interface Bronchial Epithelial Model for Realistic, Repeated Inhalation Exposure to Airborne Particles for Toxicity Testing
Published on: May 13, 2020
RAGE/NF-κB signaling mediates paraquat-induced alveolar-capillary barrier injury in a human alveolar
Siyi Zhang1, Shuzhen Hu2, Hongzhe Liu3
1Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China; Department of Ultrasonography, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
Paraquat herbicide causes lung injury by damaging the alveolar-capillary barrier. A new model shows RAGE/NF-κB pathway activation in lung cells, suggesting a therapeutic target for paraquat poisoning.
Area of Science:
- Pulmonary Toxicology
- Cellular and Molecular Biology
- Biomedical Engineering
Background:
- Paraquat (PQ) is a toxic herbicide causing fatal lung injury with no specific antidote.
- Existing models fail to replicate the lung's air-liquid interface (ALI) and alveolar-capillary barrier.
- Understanding PQ's pathogenic mechanisms is crucial for developing treatments.
Purpose of the Study:
- To develop an Alveolar Microphysiological System (AMS) to model PQ-induced lung injury.
- To investigate cell-type-specific responses to PQ exposure at the ALI.
- To identify potential therapeutic targets for PQ poisoning.
Main Methods:
- Co-culture of alveolar epithelial cells (EPCs) and pulmonary microvascular endothelial cells (EDCs) in an AMS with ALI.
- Bulk and single-cell RNA sequencing (scRNA-seq) to analyze gene expression changes.
- Functional assays to assess barrier integrity and RAGE inhibitor efficacy.
Main Results:
- The AMS accurately mimicked PQ-induced lung injury, including increased barrier permeability and junction disruption.
- PQ activated RAGE/NF-κB signaling and inflammation in EPCs but suppressed it in EDCs.
- FPS-ZM1, a RAGE inhibitor, restored barrier function and cell junction integrity.
Conclusions:
- The AMS is a valuable platform for studying PQ lung injury and developing therapies.
- RAGE/NF-κB signaling has cell-type-specific roles in PQ-induced pulmonary toxicity.
- Targeting the RAGE/NF-κB pathway offers a promising therapeutic strategy for paraquat poisoning.
