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MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury
To investigate the role of miR-146 and its possible relationship with MALAT1 in LPS-induced inflammation in human microvascular endothelial cells (HMECs), HMEC-1 cells were treated with LPS to construct an inflammatory injury cell model, and the cell viability, TNF-α and IL-6 secretion and the expre...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900645/ https://www.ncbi.nlm.nih.gov/pubmed/31291804 http://dx.doi.org/10.1177/1753425919861427 |
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author | Feng, Lin-Lin Xin, Wei-Na Tian, Xiu-Li |
author_facet | Feng, Lin-Lin Xin, Wei-Na Tian, Xiu-Li |
author_sort | Feng, Lin-Lin |
collection | PubMed |
description | To investigate the role of miR-146 and its possible relationship with MALAT1 in LPS-induced inflammation in human microvascular endothelial cells (HMECs), HMEC-1 cells were treated with LPS to construct an inflammatory injury cell model, and the cell viability, TNF-α and IL-6 secretion and the expression levels of VCAM-1, SELE and ICAM-1 were analysed as markers of inflammatory injury. The regulation mechanisms of miR-146 interacted with MALAT1 and the downstream NF-κB signalling were also verified by dual-luciferase assay and knockdown technology. LPS significantly decreased the cell viability, increased levels of VCAM-1, SELE and ICAM-1 and also up-regulated miR-146a/b, TNF-α and IL-6 in a dose-dependent manner. Over-expression of miR-146a resulted in down-regulation of TNF-α and IL-6, as well as VCAM-1, SELE and ICAM-1, while inhibition of miR-146a led to opposite results. The dual-luciferase reporter assay showed both miR-146a and miR-146b directly targeted and negatively regulated the expression of MALAT1. Silencing of MALAT1 suppressed LPS-induced NF-κB activation and TNF-α and IL-6 secretion, reducing the cell inflammatory injury, but these changes were reversed after combined treatment with miR-146a inhibitor. Taken together, we demonstrate that miR-146 protects HMECs against inflammatory injury by inhibiting NF-κB activation. This process is modulated by MALAT1. |
format | Online Article Text |
id | pubmed-6900645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-69006452019-12-13 MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury Feng, Lin-Lin Xin, Wei-Na Tian, Xiu-Li Innate Immun Original Articles To investigate the role of miR-146 and its possible relationship with MALAT1 in LPS-induced inflammation in human microvascular endothelial cells (HMECs), HMEC-1 cells were treated with LPS to construct an inflammatory injury cell model, and the cell viability, TNF-α and IL-6 secretion and the expression levels of VCAM-1, SELE and ICAM-1 were analysed as markers of inflammatory injury. The regulation mechanisms of miR-146 interacted with MALAT1 and the downstream NF-κB signalling were also verified by dual-luciferase assay and knockdown technology. LPS significantly decreased the cell viability, increased levels of VCAM-1, SELE and ICAM-1 and also up-regulated miR-146a/b, TNF-α and IL-6 in a dose-dependent manner. Over-expression of miR-146a resulted in down-regulation of TNF-α and IL-6, as well as VCAM-1, SELE and ICAM-1, while inhibition of miR-146a led to opposite results. The dual-luciferase reporter assay showed both miR-146a and miR-146b directly targeted and negatively regulated the expression of MALAT1. Silencing of MALAT1 suppressed LPS-induced NF-κB activation and TNF-α and IL-6 secretion, reducing the cell inflammatory injury, but these changes were reversed after combined treatment with miR-146a inhibitor. Taken together, we demonstrate that miR-146 protects HMECs against inflammatory injury by inhibiting NF-κB activation. This process is modulated by MALAT1. SAGE Publications 2019-07-10 2019-10 /pmc/articles/PMC6900645/ /pubmed/31291804 http://dx.doi.org/10.1177/1753425919861427 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Feng, Lin-Lin Xin, Wei-Na Tian, Xiu-Li MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury |
title | MALAT1 modulates miR-146’s protection of microvascular endothelial
cells against LPS-induced NF-κB activation and inflammatory
injury |
title_full | MALAT1 modulates miR-146’s protection of microvascular endothelial
cells against LPS-induced NF-κB activation and inflammatory
injury |
title_fullStr | MALAT1 modulates miR-146’s protection of microvascular endothelial
cells against LPS-induced NF-κB activation and inflammatory
injury |
title_full_unstemmed | MALAT1 modulates miR-146’s protection of microvascular endothelial
cells against LPS-induced NF-κB activation and inflammatory
injury |
title_short | MALAT1 modulates miR-146’s protection of microvascular endothelial
cells against LPS-induced NF-κB activation and inflammatory
injury |
title_sort | malat1 modulates mir-146’s protection of microvascular endothelial
cells against lps-induced nf-κb activation and inflammatory
injury |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900645/ https://www.ncbi.nlm.nih.gov/pubmed/31291804 http://dx.doi.org/10.1177/1753425919861427 |
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