MiR-374a-5p alleviates sepsis-induced acute lung injury by targeting ZEB1 via the p38 MAPK pathway.

Abstract

The aim of the present study was to investigate the effects of microRNA (miR)-374a-5p on sepsis-induced acute lung injury (ALI) and the associated mechanism. Lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMVECs) were used to construct the cellular model of sepsis. A luciferase reporter assay was performed to confirm the association between miR-374a-5p and zinc finger E-box binding homeobox 1 (ZEB1). Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to assess the relative expression of miR-374a-5p, ZEB1 and apoptosis-related proteins. Cell viability and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry, respectively. Enzyme-linked immunosorbent assays were used to evaluate inflammatory cytokines. The results revealed that miR-374a-5p was downregulated in sepsis patients and LPS-treated HPMVECs. Upregulation of miR-374a-5p alleviated LPS-triggered cell injury in HPMVECs, as evidenced by restoration of cell viability, and inhibition of apoptosis and the production of proinflammatory cytokines. In addition, ZEB1 was revealed to be a downstream target of miR-374a-5p, and overexpression of ZEB1 could reverse the anti-apoptotic and anti-inflammatory effects of miR-374a-5p on an LPS-induced sepsis cell model. Moreover, miR-374a-5p-induced protective effects involved the p38 MAPK signaling pathway. Collectively, miR-374a-5p exerted a protective role in sepsis-induced ALI by regulating the ZEB1-mediated p38 MAPK signaling pathway, providing a potential target for the diagnosis and treatment of sepsis.