MicroRNA-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression

Abstract

Acute lung injury is a critical acute respiratory distress syndrome (ARDS) with high morbidity and mortality. MicroRNAs (miRNAs) have been demonstrated to play important roles regulating acute lung injury development. In this study, we found that the expression of miR-598 was significantly upregulated in the lung tissues of mice with LPS-induced acute lung injury. Both loss-of function and gain-of-function studies were performed to evaluate the function of miR-598 in acute lung injury. The results showed that inhibition of miR-598 attenuated inflammatory response, oxidative stress and lung injury in mice treated with LPS, while overexpression of miR-598 exacerbated the LPS-induced acute lung injury. Mechanistically, transcription factor Early B-cell Factor-1 (Ebf1) was predicted and validated as a downstream target of miR-598. Overexpression of Ebf1 attenuated LPS-induced production of inflammatory cytokine TNF-α and IL-6, ameliorated LPS-induced oxidative stress, promoted proliferation and inhibited apoptosis in murine lung epithelial − 15 (MLE-15) cells. Moreover, we demonstrated that Ebf1 knockdown abolished the protective effect of miR-598 inhibition in MLE-15 cells. In summary, miR-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression, which might provide potential therapeutic treatment for acute lung injury.

Identification of endothelial and mesenchymal FOXF1 enhancers involved in alveolar capillary dysplasia

“…EBF1 was recently identified as an important transcription factor in pulmonary pericytes 48 . EBF1 was also shown to be critical for B-lymphocyte differentiation 49 and during lung repair after LPS-mediated injury 50 . Our findings indicate that FEL2 and FEL4 mesenchymal enhancers in FOXF1 promoter are differentially regulated by GLI and EBF1 during lung development.…”