miR‑374a‑5p alleviates sepsis‑induced acute lung injury by targeting ZEB1 via the p38 MAPK pathway
Affiliations: Department of Intensive Care Unit, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750002, P.R. China, Department of Orthopedics, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
- Published online on: July 12, 2022 https://doi.org/10.3892/etm.2022.11501
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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.