Zilong Lu1, Haojie Feng1, Xiaokang Shen1, Ruyuan He1, Heng Meng1, Weichen Lin1, Qing Geng2. 1. Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. 2. Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: szgqing@126.com.
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.
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.
Authors: Felipe Muñoz-Córdova; Carolina Hernández-Fuentes; Camila Lopez-Crisosto; Mayarling F Troncoso; Ximena Calle; Alejandra Guerrero-Moncayo; Luigi Gabrielli; Mario Chiong; Pablo F Castro; Sergio Lavandero Journal: Front Cardiovasc Med Date: 2021-12-23