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

Li Wei; Jiwei Li; Zhijun Han; Zhong Chen; Quan Zhang

doi:10.1016/j.omtn.2019.05.009

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

Mol Ther Nucleic Acids. 2019 Dec 6:18:285-297. doi: 10.1016/j.omtn.2019.05.009. Epub 2019 May 28.

Authors

Li Wei¹, Jiwei Li², Zhijun Han¹, Zhong Chen¹, Quan Zhang¹

Affiliations

¹ Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University and People's Hospital of Henan University, Zhengzhou 450003, P.R. China.
² Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University and People's Hospital of Henan University, Zhengzhou 450003, P.R. China. Electronic address: facefuture00114321@163.com.

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.

Keywords: H3K27 acetylation; chemotaxis of neutrophils; inflammatory injury; interleukin-8; long non-coding RNA; lung transplant ischemia-reperfusion; metastasis-associated lung adenocarcinoma transcript 1; p300; pulmonary epithelial cells.