MiR-122-5p protects against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells

Abstract

Aims: The aim of this study was to explore the role of miR-122-5p in acute lung injury.

Materials and methods: Mice were subjected to intratracheal injection of lipopolysaccharide to establish an acute lung injury model. The mice also received miR-122-5p antagonist and mimic via injection to inhibit or overexpress miR-122-5p in the lung tissue, respectively. In an in vitro experiment, we isolated primary mouse lung microvascular endothelial cells and established a cell injury model via lipopolysaccharide treatment.

Key findings: Mice injected with an miR-122-5p antagonist exhibited reduced lung injury, inflammation and oxidative stress, while mice injected with a miR-122-5p mimic exhibited exaggerated lung injury, inflammation and oxidative stress. In an in vitro experiment, we found that the miR-122-5p antagonist suppressed lipopolysaccharide-induced inflammation, apoptosis and oxidative stress. Moreover, miR-122-5p regulated the promoter activity of DUSP4, which negatively regulated ERK1/2 signaling. The use of DUSP4 siRNA counteracted the effects of the miR-122-5p antagonist.

Significance: Taken together, these results show that miR-122-5p protected against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells. MiR-122-5p antagonism may be a promising treatment method for acute lung injury.

Keywords: Acute lung injury; DUSP4; ERK1/2; Endothelial cells; miR-122-5p.