Research Paper Volume 12, Issue 8 pp 6570—6585
Long non-coding RNA MALAT1 exacerbates acute respiratory distress syndrome by upregulating ICAM-1 expression via microRNA-150-5p downregulation
- 1 Department of Respiratory Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
- 2 Department of Anatomy, Nursing College of Zhengzhou University, Zhengzhou 450052, P.R. China
- 3 Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
Received: November 28, 2019 Accepted: March 9, 2020 Published: April 21, 2020https://doi.org/10.18632/aging.102953
How to Cite
Copyright © 2020 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury in which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. This study investigated the role of lung adenocarcinoma transcript 1 (MALAT1) in ARDS and the underlying mechanism involved. The expression of MALAT1, microRNA-150-5p (miR-150-5p), and intercellular adhesion molecule-1 (ICAM-1) was determined in ARDS patients and lipopolysaccharide (LPS)-treated human pulmonary microvascular endothelial cells (HPMECs). Next, the interactions among MALAT1, miR-150-5p, and ICAM-1 were explored. Gain- or loss-of-function experiments in HPMECs were employed to determine cell apoptosis and inflammation. Furthermore, a mouse xenograft model of ARDS was established in order to verify the function of MALAT1 in vivo. MALAT1 and ICAM-1 were upregulated, while miR-150-5p was downregulated in both ARDS patients and LPS-treated HPMECs. MALAT1 upregulated ICAM-1 expression by competitively binding to miR-150-5p. MALAT1 silencing or miR-150-5p overexpression was shown to suppress HPMEC apoptosis, decrease the expressions of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) and E-selectin in HPMECs, as well as alleviated lung injury in nude mice. These findings demonstrated that MALAT1 silencing can potentially suppress HPMEC apoptosis and alleviate lung injury in ARDS via miR-150-5p-targeted ICAM-1, suggestive of a novel therapeutic target for ARDS.