AUTHOR=Cai Quan , Jin Yan , Jia Ziyi , Liu Zhi 

TITLE=Paraquat Induces Lung Injury via miR-199-Mediated SET in a Mouse Model

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.856441

DOI=10.3389/fphar.2022.856441

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To explore the molecular mechanism of lung injury caused by paraquat (PQ) poisoning by investigating miR-199-mediated SET.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> Paraquat induces ALI by affecting miR-199-mediated SET.</p>