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Life Sci ; 242: 117213, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31881228

RESUMEN

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung injury disease with high morbidity and mortality. However, the underlying pathogenic mechanism remains unknown. In this study, lipopolysaccharide (LPS)-stimulated alveolar epithelial cells were used to mimic the inflammatory pathogenesis of ARDS in vitro. We here investigated the role of miR-424 in LPS-stimulated alveolar epithelial cells and found it to be substantially downregulated. Overexpression of miR-424 inhibited apoptosis and inflammation in LPS-stimulated alveolar epithelial cells, and the miR-424 inhibitor exhibited the opposite effect. A bioinformatic analysis revealed a potential binding site of miR-424 in the 3'-UTR of fibroblast growth factor 2 (FGF2). A luciferase reporter assay suggested that miR-424 targeted FGF2 in alveolar epithelial cells. The level of FGF2 protein was inhibited by miR-424 mimic, whereas was significantly upregulated after miR-424 suppression in LPS-stimulated alveolar epithelial cells. MiR-424 also exhibited the protective role in LPS-induced apoptosis and inflammation by directly targeting FGF2 via the NF-κB pathway. In conclusion, our results demonstrate that miR-424 had a protective role in LPS-induced apoptosis and inflammation of alveolar epithelial cells by targeting FGF2 via regulating NF-κB pathway. This might contribute novel evidence to help identify a therapeutic target for treating ARDS.


Asunto(s)
Células A549/metabolismo , Apoptosis/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/fisiología , Inflamación/fisiopatología , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , FN-kappa B/metabolismo , Alveolos Pulmonares/metabolismo , Mucosa Respiratoria/metabolismo , Transducción de Señal , Células A549/fisiología , Apoptosis/fisiología , Western Blotting , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Inflamación/metabolismo , MicroARNs/fisiología , Alveolos Pulmonares/citología , Alveolos Pulmonares/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Mucosa Respiratoria/citología , Mucosa Respiratoria/fisiología , Transducción de Señal/fisiología
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