MicroRNA‐339‐3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis‐associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway

摘要

Abstract Severe acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP‐ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP‐ALI. This study aims to define the role of miR‐339‐3p in SAP‐ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR‐339‐3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF‐α, IL‐6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT‐qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP‐ALI mice had decreased survival rate, increased levels of TNF‐α, IL‐6, AMS, MPO, and Schmidt scores. miR‐339‐3p was poorly expressed in lung tissue of SAP‐ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR‐339‐3p. miR‐339‐3p inhibited the relative expression of the Akt/mTOR signaling pathway‐related proteins, alleviated inflammation and edema of SAP‐ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR‐339‐3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP‐ALI mice.