MiR-297 alleviates LPS-induced A549 cell and mice lung injury via targeting cyclin dependent kinase 8
| Autor: | Pibao Li, Xueqin Xi, Na Liu, Yanfen Yao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Lipopolysaccharide Acute Lung Injury Immunology Apoptosis Lung injury Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans Immunology and Allergy Gene silencing Phosphorylation Pharmacology A549 cell Respiratory Distress Syndrome Cell growth Transcription Factor RelA respiratory system Cyclin-Dependent Kinase 8 respiratory tract diseases Disease Models Animal MicroRNAs IκBα 030104 developmental biology chemistry A549 Cells 030220 oncology & carcinogenesis Cancer research Signal Transduction |
| Zdroj: | International Immunopharmacology. 80:106197 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2020.106197 |
| Popis: | In recent decades, microRNAs (miRNAs) have been reported to play an important role in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To explore the underlying mechanisms of miR-297 in ALI/ARDS, we investigated its role in lipopolysaccharide (LPS)-induced A549 cell and mice lung injury model. We found that the expression of miR-297 decreased in LPS-induced A549 cells or serum of ALI/ARDS mice. Moreover, LPS suppressed A549 cell viability, promoted apoptosis and increased the expressions of inflammatory and autophagy-related factors. Conversely, overexpression of miR-297 increased cell proliferation and reduced cell apoptosis, and alleviated inflammatory cytokines secretion and autophagy in the presence of LPS. Importantly, miR-297 directly inhibited transcription of cyclin dependent kinase 8 (CDK8) by binding to the 3'-untranslated region (3'-UTR) of CDK8 mRNA, and the expression of CDK8 was negatively regulated by miR-297. Silencing of CDK8 promoted the anti-inflammatory and anti-apoptotic effects of miR-297 in LPS-mediated A549 cells. The expressions of phosphorylated p65 (p-p65)/p65 and phosphorylated inhibitor kappa B-α (p-IκBα)/IκBα were dramatically decreased by miR-297 mimics and silencing of CDK8. In vivo, miR-297 alleviated LPS-induced inflammatory responses and lung injury in ALI/ARDS mice. In conclusion, our findings suggested that miR-297 affects nuclear factor-kappa B (NF-κB) pathway to alleviate LPS-induced A549 cell and mice lung injury via targeting CDK8 expression. |
| Databáze: | OpenAIRE |
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