Silencing of lncRNA MALAT1 Prevents Inflammatory Injury after Lung Transplant Ischemia-Reperfusion by Downregulation of IL-8 via p300.

Abstract

Ischemia-reperfusion injury is a common early complication after lung transplantation. It was reported that long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in ischemia-reperfusion injury and regulates inflammation. This study aimed to explore the role of MALAT1 in inflammatory injury following lung transplant ischemia-reperfusion (LTIR). A LTIR rat model was successfully established, with the expression of MALAT1 and interleukin-8 (IL-8) in lung tissues detected. Then, in vitro loss- and gain-of-function investigations were conducted to evaluate the effect of MALAT1 on pulmonary epithelial cell apoptosis and IL-8 expression. The relationship among MALAT1, p300, and IL-8 was tested. Moreover, a sh-MALAT1-mediated model of LTIR was established in vivo to examine inflammatory injury and chemotaxis infiltration. Both IL-8 and MALAT1 were highly expressed in LTIR. MALAT1 interacted with p300 to regulate the IL-8 expression by recruiting p300. Importantly, silencing of MALAT1 inhibited the chemotaxis of neutrophils by downregulating IL-8 expression via binding to p300. Besides, MALAT1 silencing alleviated the inflammatory injury after LTIR by downregulating IL-8 and inhibiting infiltration and activation of neutrophils. Collectively, these results demonstrated that silencing of MALAT1 ameliorated the inflammatory injury after LTIR by inhibiting chemotaxis of neutrophils through p300-mediated downregulation of IL-8, providing clinical insight for LTIR injury.

• Authors: Li Wei, Jiwei Li, Zhijun Han, Zhong Chen, Quan Zhang
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 18 Pg. 285-297 (Dec 06 2019) ISSN: 2162-2531 [Print] United States
• PMID: 31604167 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.