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

Abstract 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.