MicroRNA-877-5p alleviates ARDS via enhancing PI3K/Akt path by targeting CDKN1B both in vivo and in vitro.

Abstract Acute respiratory distress syndrome (ARDS) is a public health problem with high morbidity and mortality worldwide due to lacking known characteristic biomarkers and timely intervention. Pulmonary edema caused by inflammation and pulmonary microvascular endothelial cell disfunction is the main pathophysiological change of ARDS. Circulating microRNAs (miRNAs) are differentially expressed between subjects who did and did not develop ARDS. Many miRNAs have been exemplified to be involved in ARDS and could represent the novel therapeutic targets, but the role of microRNA-877-5p (miR-877-5p) in ARDS and its regulatory mechanisms are still unknown. Herein, we explore the underlying function of miR-877-5p toward anesis of ARDS and addressed that miRNA-877 can reduce the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 thus attenuating the damage of pulmonary microvascular endothelial cells (HPMECs). Have further evaluated the protein expression, we detected that miR-877-5p contributed to the relief of ARDS by suppressing Cyclin-dependent kinase inhibitor 1B (CDKN1B), which serves as a regulator of endothelial cell polarization and migration through phosphatidylinositol-3-kinase and AKT (PI3K/Akt) signaling pathway. Besides, we noticed that CDKN1B restrains cell differentiation by inhibiting Cdk2 (cyclin-dependent kinase 2), instead of Cdk4 (cyclin-dependent kinase 4), during which the nuclear translocation of CDKN1B may participate. Together, our works testified that miR-877-5p might suppress inflammatory responses and promote HPMECs regeneration via targeting CDKN1B by modulation of Cdk2 and PI3K/Akt path. These molecules likely modulating ARDS progression may inform biomarkers and therapeutic development.