MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway

Yang,Guang; Zhao,Yuan

doi:10.3892/etm.2020.9584

MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway

Authors:
- Guang Yang
- Yuan Zhao
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Affiliations: Department of Pediatrics, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Neonatal Internal Medicine, Shanxi Children's Hospital, Taiyuan, Shanxi 030013, P.R. China
Published online on: December 17, 2020 https://doi.org/10.3892/etm.2020.9584
Article Number: 152
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a main reason for neonatal death. Studying the molecular mechanism behind neonatal ALI is critical for the development of therapeutic strategies. The present study explored microRNA (miR)‑490-3p-mediated regulatory effects on lipopolysaccharide (LPS)-induced neonatal ALI. Initially, LPS (10 mg/kg body weight) was injected to 3-8 day old neonatal SD rats to induce ALI, and LPS (100 ng/ml) was used to treat lung epithelial cells to construct an ALI model in vitro. Next, miR-490-3p, pro-inflammatory factors (that included IL-1β, IL-6 and TNFα), interleukin 1 receptor associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6) mRNA expression levels in lung tissues and epithelial cells were assessed via reverse transcription-quantitative PCR. In addition, miR-490-3p mimics were adopted to construct its overexpressed cell model, and Cell Counting Kit-8 and BrdU assays were conducted to assess cell viability. Furthermore, the miR-490-3p target, IRAK was predicted by bioinformatics analysis and verified via dual-luciferase reporter gene assay. The results revealed that miR-490-3p was markedly downregulated in an LPS-induced rat ALI model, while IL-1β, IL-6, TNFα, IRAK1 and TRAF6 were all upregulated and negatively correlated with miR‑490-3p expression. Moreover, overexpressed miR-490-3p significantly inhibited LPS-induced lung epithelial cell injury and inflammatory response. Mechanistically, miR-490-3p targeted and attenuated IRAK1 expression, which thus inactivated the LPS-mediated TRAF6/NF-κB pathway. Overall, the present study indicated that miR-490-3p overexpression significantly inhibited LPS-induced ALI and inflammatory responses by restricting the IRAK1/TRAF6 pathway.

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