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MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway
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....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792502/ https://www.ncbi.nlm.nih.gov/pubmed/33456519 http://dx.doi.org/10.3892/etm.2020.9584 |
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author | Yang, Guang Zhao, Yuan |
author_facet | Yang, Guang Zhao, Yuan |
author_sort | Yang, Guang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7792502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-77925022021-01-14 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 Exp Ther Med Articles 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. D.A. Spandidos 2021-02 2020-12-17 /pmc/articles/PMC7792502/ /pubmed/33456519 http://dx.doi.org/10.3892/etm.2020.9584 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Yang, Guang Zhao, Yuan MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title | MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title_full | MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title_fullStr | MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title_full_unstemmed | MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title_short | MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway |
title_sort | microrna-490-3p inhibits inflammatory responses in lps-induced acute lung injury of neonatal rats by suppressing the irak1/traf6 pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792502/ https://www.ncbi.nlm.nih.gov/pubmed/33456519 http://dx.doi.org/10.3892/etm.2020.9584 |
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