MicroRNA-486-5p Promotes Acute Lung Injury via Inducing Inflammation and Apoptosis by Targeting OTUD7B
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ORIGINAL ARTICLE
MicroRNA-486-5p Promotes Acute Lung Injury via Inducing Inflammation and Apoptosis by Targeting OTUD7B Qiang Luo,1 Jun Zhu,2 Qian Zhang,1 Jie Xie,1 Chengla Yi,1 and Tianyu Li
1,3
Abstract— The aim of this article is to study the effect of miR-486-5p in acute lung injury
(ALI). MiR-486-5p expression in peripheral blood was determined in ALI patients and healthy volunteers by qRT-PCR. ALI mouse model were reproduced by LPS treatment, and miR-486-5p NC and miRNA-486 inhibitors were injected through trachea. ALI patients’ peripheral blood and LPS-induced acute lung injury in mice had significantly higher miR486-5p levels than control subjects. Inhibition of miR-486-5p by injection with antagomiR486-5p markedly reduced LPS-induced lung inflammation. Moreover, knockdown of miR486-5p can reduce protects A549 cell against LPS-induced injury and its corresponding inflammatory response. In addition, Mechanistic analysis indicated that miR-486-5p on the occurrence of ALI is related to the inhibition of OTUD7B activity, which induces the downregulation of inflammatory in ALI. Our results identified miR-486-5p independently associated with ALI. miR-486-5p can mediate the formation of ALI by promoting inflammation. KEY WORDS: Acute lung injury; miR-486-5p; OTUD7B; Inflammation; LPS; Apoptosis.
INTRODUCTION
Qiang Luo and Jun Zhu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-020-01183-3) contains supplementary material, which is available to authorized users. 1
Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Department of Anesthesiology, The Fourth Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 To whom correspondence should be addressed at Trauma Center/ Department of Emergency and Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. E-mail: [email protected]
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the clinical common severe acute disease with a high death rate, which is caused by complicated pathogenesis and developing rapidly [25, 28]. The main pathological features of ALI are increased pulmonary vascular permeability, exudation of protein-rich fluid in alveolar cavity, pulmonary edema, and hyaline membrane formation [2, 9, 24]. Lipopolysaccharide (LPS) is one of the important risk factors of ALI and can lead to acute diffuse damage of alveolar capillary endothelial cells, alveolar epithelial cells, and pulmonary stroma [6]. Its essence is the activation and infiltration of various inflammatory cells in the lung and the release of a series of inflammatory mediators, resulting in lung injury. At the same time, more inflammatory cells are activated and more
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