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Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis
Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS proce...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675692/ https://www.ncbi.nlm.nih.gov/pubmed/29152140 http://dx.doi.org/10.18632/oncotarget.21408 |
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author | Lv, Guangxin Zhu, Hongmei Li, Cai Wang, Jingyu Zhao, Dandan Li, Shuyao Ma, Le Sun, Guohua Li, Fang Zhao, Ying Gao, Ying |
author_facet | Lv, Guangxin Zhu, Hongmei Li, Cai Wang, Jingyu Zhao, Dandan Li, Shuyao Ma, Le Sun, Guohua Li, Fang Zhao, Ying Gao, Ying |
author_sort | Lv, Guangxin |
collection | PubMed |
description | Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients’ serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time. |
format | Online Article Text |
id | pubmed-5675692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56756922017-11-18 Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis Lv, Guangxin Zhu, Hongmei Li, Cai Wang, Jingyu Zhao, Dandan Li, Shuyao Ma, Le Sun, Guohua Li, Fang Zhao, Ying Gao, Ying Oncotarget Research Paper Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients’ serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time. Impact Journals LLC 2017-09-30 /pmc/articles/PMC5675692/ /pubmed/29152140 http://dx.doi.org/10.18632/oncotarget.21408 Text en Copyright: © 2017 Lv et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Lv, Guangxin Zhu, Hongmei Li, Cai Wang, Jingyu Zhao, Dandan Li, Shuyao Ma, Le Sun, Guohua Li, Fang Zhao, Ying Gao, Ying Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title | Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title_full | Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title_fullStr | Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title_full_unstemmed | Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title_short | Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis |
title_sort | inhibition of il-8-mediated endothelial adhesion, vsmcs proliferation and migration by sirna-tmem98 suggests tmem98's emerging role in atherosclerosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675692/ https://www.ncbi.nlm.nih.gov/pubmed/29152140 http://dx.doi.org/10.18632/oncotarget.21408 |
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