MiR-34a-5p inhibition attenuates LPS-induced endothelial cell injury by targeting FOXM1

F.-M. Zhang, W.-H. Zheng, H.-J. Wang

The Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. onehanjun@163.com

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• Infectious Diseases

OBJECTIVE: This study aims to investigate the role of miR-34a-5p in the regulation of lipopolysaccharide (LPS)-induced injury of vascular endothelial cells (ECs).

MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were exposed to LPS to stimulate endothelial injury in vitro. miRNA microarray analysis was carried out to identify miR-34a-5p expression in HUVECs. MTT and flow cytometry analyses were used to determine cell viability and apoptosis rate, respectively. Furthermore, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blot were used to examine the factors involved in inflammation and their relative gene expression. Additionally, Matrigel-based tube formation assay was carried out to assess the vasculogenic activity of HUVECs. Luciferase reporter assay was used to analyze the possible relationship between miR-34a-5p and FOXM1.

RESULTS: MiR-34a-5p expression was significantly enhanced in HUVECs after 24 h of LPS treatment. LPS treatment led to a dramatic inhibition of cell viability, enhanced apoptosis, increased production of pro-inflammatory cytokines, and inhibited the vasculogenic activity of HUVECs. MiR-34a-5p inhibitor attenuated LPS-induced damage. MiR-34a-5p directly inhibited the expression of FOXM1, and its overexpression alleviated the protective effect of FOXM1 on cell viability, apoptosis, inflammation factor production, and vasculogenic activity. The activity of the NRF2/HO-1 pathway was inhibited by miR-34a-5p, possibly via FOXM1.

CONCLUSIONS: MiR-34a-5p inhibition attenuates LPS-induced EC injury by targeting FOXM1 via activation of the NRF2/HO-1 pathway.

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