RESUMEN
In grass carp (Ctenopharyngodon idella), septicemia is a systemic inflammatory response to bacterial infection and could be leaded to lethality. MiR-451 involved in septicemia progression has been reported. However, the underlying mechanism of miR-451 in septicemia induced inflammatory response remains to be revealed. In the present study, miR-451 was highly expressed in Aeromonas hydrophila induced CIK cells, opposite to lncRNA-ANAPC2 and lncRNA-NEFM expression. Furthermore, we found that miR-451 interacted with lncRNA-ANAPC2 and lncRNA-NEFM, also targeted the 3' UTR of npr2 and hdac8. In CIK cells, the inhibition of npr2 and hdac8 were down-regulated by lncRNA-ANAPC2 and lncRNA-NEFM knockdown, while downstream proinflammatory factors were inhibited. In a word, this study indicates that lncRNA-ANAPC2 and lncRNA-NEFM regulation the LPS-induced progression of inflammatory response by modulating miR-451/npr2/hdac8 axis.
Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , MicroARNs , ARN Largo no Codificante , Sepsis , Regiones no Traducidas 3' , Aeromonas hydrophila/fisiología , Animales , Subunidad Apc2 del Ciclosoma-Complejo Promotor de la Anafase , Carpas/genética , Carpas/metabolismo , Enfermedades de los Peces/microbiología , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Infecciones por Bacterias Gramnegativas/microbiología , Inmunidad Innata , Lipopolisacáridos/farmacología , MicroARNs/genética , ARN Largo no Codificante/genéticaRESUMEN
MicroRNA clusters are microRNAs (miRNAs) that are distributed in close proximity on chromosomes. In this study, we report a miRNA cluster identified from grass carp (Ctenopharyngodon idella), miR-462-731, which plays a positive role in host antibacterial immunity. The expression of miR-462-731 was disrupted after infection by Aeromonas hydrophila. Transcription factor ETS transcription factor ELK1 was identified to bind to the promoter of the miR-462-731 cluster and suppress its expression. In addition, miR-731 negatively regulates the expression of elk1, forms an elk1/miR-462-731 double negative feedback loop. In addition, we found that miR-731 directly targets ezrin a (ezra), participates in inducing PI3K/AKT signaling in macrophage, to induce macrophage polarization to the M1 phenotype with stronger phagocytosis. Our results demonstrate a novel elk1/miR-462-731 feedback loop. The data deepen our understanding of the relationship between macrophage polarization and phagocytosis in teleost fish.