Emodin Alleviates Acute Pancreatitis-Associated Acute Lung Injury by Inhibiting Serum Exosomal miRNA-21-3p-Induced M1 Alveolar Macrophage Polarisation

Abstract

Severe acute pancreatitis (SAP) is a common abdominal emergency in clinical practice. Approximately 20%–40% of patients with SAP will be associated with acute lung injury (SAP-ALI), which is a major cause of death. Emodin (EMO) is a naturally occurring anthraquinone derivative with various pharmacological properties. EMO has a therapeutic effect on SAP-ALI; however, the underlying mechanism remains unclear. Exosomes mediate intercellular communication in disease progression. Therefore, this study aimed to explore the role of serum exosomes in SAP-ALI and the potential mechanisms by which EMO regulates the composition of exosomes for treatment. miR-21-3p was highly expressed in serum exosomes of the SAP group and exacerbated M1 polarisation of alveolar macrophages (AMs). EMO treatment reduced serum exosomal miR-21-3p and relatively attenuated M1 polarisation. Transfection with an miR-21-3p inhibitor attenuated LPS-induced M1 polarisation of AMs in vitro; however, its effects were partially reversed when the downstream target gene PTEN was knocked down simultaneously. This study suggests that EMO reduced the enrichment of miR-21-3p in serum-derived exosomes of rats with SAP, inhibiting the M1 polarisation of AMs caused by the transfer of miR-21-3p through the exosome pathway. This mechanism is related to miR-21-3p targeting of the PTEN/PI3K/AKT signalling pathway.