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A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression
Mixed-lineage kinase domain-like protein (MLKL) is known as the terminal executor of necroptosis. However, its function outside of necroptosis is still not clear. Herein, we demonstrate that MLKL promotes vascular inflammation by regulating the expression of adhesion molecules ICAM1, VCAM1, and E-se...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181788/ https://www.ncbi.nlm.nih.gov/pubmed/32332696 http://dx.doi.org/10.1038/s41419-020-2483-3 |
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author | Dai, Jialin Zhang, Chonghe Guo, Lin He, Hao Jiang, Kai Huang, Yingying Zhang, Xixi Zhang, Haibing Wei, Wu Zhang, Yaoyang Lu, Lihua Hu, Junhao |
author_facet | Dai, Jialin Zhang, Chonghe Guo, Lin He, Hao Jiang, Kai Huang, Yingying Zhang, Xixi Zhang, Haibing Wei, Wu Zhang, Yaoyang Lu, Lihua Hu, Junhao |
author_sort | Dai, Jialin |
collection | PubMed |
description | Mixed-lineage kinase domain-like protein (MLKL) is known as the terminal executor of necroptosis. However, its function outside of necroptosis is still not clear. Herein, we demonstrate that MLKL promotes vascular inflammation by regulating the expression of adhesion molecules ICAM1, VCAM1, and E-selectin in endothelial cells (EC). MLKL deficiency suppresses the expression of these adhesion molecules, thereby reducing EC-leukocyte interaction in vitro and in vivo. Mechanistically, we show that MLKL interacts with RBM6 to promote the mRNA stability of adhesion molecules. In conclusion, this study identified a novel role of MLKL in regulating endothelial adhesion molecule expression and local EC-leukocyte interaction during acute inflammation. |
format | Online Article Text |
id | pubmed-7181788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71817882020-04-29 A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression Dai, Jialin Zhang, Chonghe Guo, Lin He, Hao Jiang, Kai Huang, Yingying Zhang, Xixi Zhang, Haibing Wei, Wu Zhang, Yaoyang Lu, Lihua Hu, Junhao Cell Death Dis Article Mixed-lineage kinase domain-like protein (MLKL) is known as the terminal executor of necroptosis. However, its function outside of necroptosis is still not clear. Herein, we demonstrate that MLKL promotes vascular inflammation by regulating the expression of adhesion molecules ICAM1, VCAM1, and E-selectin in endothelial cells (EC). MLKL deficiency suppresses the expression of these adhesion molecules, thereby reducing EC-leukocyte interaction in vitro and in vivo. Mechanistically, we show that MLKL interacts with RBM6 to promote the mRNA stability of adhesion molecules. In conclusion, this study identified a novel role of MLKL in regulating endothelial adhesion molecule expression and local EC-leukocyte interaction during acute inflammation. Nature Publishing Group UK 2020-04-24 /pmc/articles/PMC7181788/ /pubmed/32332696 http://dx.doi.org/10.1038/s41419-020-2483-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dai, Jialin Zhang, Chonghe Guo, Lin He, Hao Jiang, Kai Huang, Yingying Zhang, Xixi Zhang, Haibing Wei, Wu Zhang, Yaoyang Lu, Lihua Hu, Junhao A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title | A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title_full | A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title_fullStr | A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title_full_unstemmed | A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title_short | A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression |
title_sort | necroptotic-independent function of mlkl in regulating endothelial cell adhesion molecule expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181788/ https://www.ncbi.nlm.nih.gov/pubmed/32332696 http://dx.doi.org/10.1038/s41419-020-2483-3 |
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