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Paraquat Induces Lung Injury via miR-199-Mediated SET in a Mouse Model
Quan Cai1, Yan Jin1, Ziyi Jia1
1Department of Emergency, The First Hospital of China Medical University, Shenyang, China.
Abstract:
Objective: To explore the molecular mechanism of lung injury caused by paraquat (PQ) poisoning by investigating miR-199-mediated SET. Methods: A paraquat poisoning model was established in C57BL/6 male mice via intraperitoneal injection of paraquat. The mice were transfected with miR-199 siRNA and or mimic. After 14 days of treatment, pathophysiological changes of the lung were observed and lung tissue was analyzed via Hematoxylin-Eosin staining. The levels of miR-199, SETs, surfactant protein SP-A and SP-B, and inflammatory and oxidative factors were analyzed by qPCR, Western Blot, and ELISA kits. Results: A acute lung-injury (ALI) model was established using PQ treatment and confirmed with edema of pulmonary endothelium with low electronic density of endothelial cytoplasm, presence of protein-rich fluid, and numerous erythrocytes in alveolar space, concentric figures of damaged tubular myelin, alveolar destruction, and increase in inflammatory cell numbers. Compared with the control group, miR-199 and SET levels were reduced in the PQ-treated group. miR-199 siRNA increased the SET level, inflammatory and oxidative levels, and reduced the levels of SP-A and SP-B, and miR-199 mimic reduced the SET level, inflammatory and oxidative levels, and increased the levels of SP-A and SP-B. PQ treatment reduced miR-199 level. Conclusion: Paraquat induces ALI by affecting miR-199-mediated SET.
Insights
Paraquat poisoning causes acute lung injury (ALI) by reducing miR-199 levels, which impacts SET expression. This study reveals a novel molecular mechanism for paraquat-induced lung damage.
Area of Science:
- Toxicology
- Molecular Biology
- Pulmonary Medicine
Background:
- Paraquat (PQ) is a widely used herbicide with known toxicity.
- PQ poisoning can lead to severe acute lung injury (ALI).
- The precise molecular mechanisms underlying PQ-induced ALI require further elucidation.
Purpose of the Study:
- To investigate the role of miR-199 in the molecular pathogenesis of paraquat-induced lung injury.
- To explore the relationship between miR-199 and SET expression in the context of PQ poisoning.
- To elucidate the potential therapeutic target of miR-199 in paraquat-induced ALI.
Main Methods:
- Establishment of a paraquat poisoning mouse model via intraperitoneal injection.
- Transfection of mice with miR-199 small interfering RNA (siRNA) or mimic.
- Assessment of lung injury through histological analysis (Hematoxylin-Eosin staining) and measurement of molecular markers (qPCR, Western Blot, ELISA) including miR-199, SET, SP-A, SP-B, and inflammatory/oxidative factors.
Main Results:
- Paraquat treatment successfully induced ALI in mice, characterized by pulmonary edema, alveolar destruction, and increased inflammatory cell infiltration.
- PQ exposure led to decreased levels of miR-199 and SET in lung tissue.
- Modulation of miR-199 levels inversely affected SET expression, inflammatory markers, oxidative stress, and surfactant proteins (SP-A, SP-B), indicating a regulatory role.
Conclusions:
- Paraquat induces acute lung injury by downregulating miR-199.
- The observed lung injury is mediated, at least in part, by the miR-199-mediated regulation of SET.
- Targeting the miR-199/SET pathway presents a potential therapeutic strategy for paraquat poisoning.
