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Knockdown of circ_0001679 alleviates lipopolysaccharide-induced MLE-12 lung cell injury by regulating the miR-338-3p/ mitogen-activated protein kinase 1 axis
The upregulation of circ_0001679 was reported in lipopolysaccharide (LPS)-induced lung injury mouse model, but its functional roles and mechanisms in LPS-induced lung injury remain to be investigated. In this study, we aimed to explore the potential role of circ_0001679 in septic acute lung injury....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973724/ https://www.ncbi.nlm.nih.gov/pubmed/35264058 http://dx.doi.org/10.1080/21655979.2022.2034564 |
Sumario: | The upregulation of circ_0001679 was reported in lipopolysaccharide (LPS)-induced lung injury mouse model, but its functional roles and mechanisms in LPS-induced lung injury remain to be investigated. In this study, we aimed to explore the potential role of circ_0001679 in septic acute lung injury. We initially established an in vitro lung cell injury model using LPS-treated MLE-12 cells. siRNAs targeting circRNA_0001679 were employed to stably knock down circRNA_0001679, followed by functional assays to investigate the effect of circRNA_0001679 silencing. The levels of inflammatory cytokines such as IL-6, IL-β and TNF-α (Tumor necrosis factor-α) were detected by ELISA (Enzyme-linked immunosorbent assay). Meanwhile, protein levels of Bcl-2, cleaved-caspase 3, Bax, and MAPK1 (Mitogen-Activated Protein Kinase 1) proteins expression level were measured by Western blot. We found that Circ_0001679 was upregulated in LPS-induced MLE-12 cells, and silencing circ_0001679 attenuated the growth inhibition and suppressed apoptosis induced by LPS. Circ_0001679 knockdown also lowered levels of IL-6, IL-β and TNF-α, and prevent the activation of cleaved-caspase 3 protein. We further revealed that circ_0001679 functioned as a sponge of miR-338-3p to negatively regulate miR-338-3p activity. miR-338-3p downregulated its downstream target MAPK1, while the upregulation of circ_0001679 maintained a high-level expression of MAPK1 by suppressing miR-338-3p. Collectively, our study indicates that circ_0001679/miR-338-3p/MAPK1 axis may play an important role in the pathogenesis of acute lung injury (ALI). |
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