Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway

Changfu Xu¹, Lei Chong², Gang Yu¹ , Hailin Zhang¹

¹Department of Pediatric Respiratory; ²Institute of Pediatrics, National Key Clinical Specialty of Pediatric Respiratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325027, China.

For correspondence:- Gang Yu Email: GangYugkl@163.com Tel:+8657788002125

Accepted: 26 January 2020 Published: 29 April 2020

Citation: Xu C, Chong L, Yu G, Zhang H. MiR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway. Trop J Pharm Res 2020; 19(4):676-682 doi: 10.4314/tjpr.v19i4.1

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the protective effect of miR-574-5p pretreatment against acute lung injury (ALI) induced by sepsis.

Methods: A male C57BL/6 mouse model of sepsis-induced ALI was established by cecal ligation and puncture (CLP) and treated with miR-574-5p agomir (intravenous injection, 80 mg/kg per day, 3 days). After that, blood and lung samples were obtained for histopathological observation. Myeloperoxidase (MPO) activity, inflammatory cell infiltration, and cytokine expression were analyzed. The target gene of miR-574-5p was predicted using TargetScan prediction, and verified by luciferase assay and western blot.

Results: In sepsis-induced ALI mice model, downregulation of miR-574-5p was observed. Pretreatment of miR-574-5p significantly alleviated ALI by suppressing histological damage, and reducing MPO activity and inflammatory cell infiltration, as well as decreasing cytokine expression. The underlying mechanism was that miR-574-5p targeted TNF receptor associated factor 6 (TRAF6) and suppressed the downstream NF-κB pathway. Moreover, TRAF6 overexpression reversed the effects of miR-574-5p on ALI.

Conclusion: MiR-574-5p pretreatment suppresses inflammatory responses, thus reducing lung injury induced by sepsis in mice, partly via the regulation of TRAF6 and NF-κB pathway. Therefore, this approach can potentially be used for the clinical management of ALI in humans

Keywords: Sepsis, Acute lung injury, MiR-574-5p, TRAF6, NF-κB pathway