MiR-146a-5p accelerates sepsis through dendritic cell activation and glycolysis via targeting ATG7.

To unveil the role and regulatory mechanism of miR-146a-5p in sepsis. A sepsis cell model was established via lipopolysaccharide (LPS)-induction in dendritic cells (DCs). The maturation of DCs was evaluated via flow cytometry. Gene expression was measured through reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The concentrations of inflammation biomarkers were revealed via enzyme-linked immunosorbent assay (ELISA). The pathological and histological changes in lungs in the sepsis mice model were analyzed via hematoxylin and eosin (H&E) staining. In this study, the miR-146a-5p level was elevated in the serum of sepsis patients and LPS-induced DCs but decreased in the serums of cured sepsis patients. Furthermore, miR-146a-5p deletion alleviated the activation of T cells and attenuated the imbalance of Th17/Treg. Besides, ATG7 was validated as a target of miR-146a-5p. ATG7 elevation enhanced lactate production and glucose uptake in LPS-triggered DCs. Additionally, upregulation of ATG7 suppressed the protein levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), phospho protein kinase B (p-AKT), and phosphorylated signal transducer and activator for transcription 3 (p-STAT3). In addition, miR-146a-5p downregulation alleviated T-cell activation, inflammation, lactate production, and glucose uptake in sepsis mice. Moreover, the lung injury due to sepsis was also attenuated as a result of miR-146a-5p silencing. MiR-146a-5p aggravates sepsis through DCs activation and glycolysis via targeting ATG7.