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The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells
BACKGROUND: Thrombomodulin (TM), a transmembrane glycoprotein highly expressed in endothelial cells (ECs), is a potent anticoagulant maintaining circulation homeostasis. Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust ex...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809974/ https://www.ncbi.nlm.nih.gov/pubmed/29439742 http://dx.doi.org/10.1186/s12929-018-0415-7 |
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author | Pai, Vincent Chunpeng Lo, I-Chung Huang, Yan wun Tsai, I-Ching Cheng, Hui-Pin Shi, Guey-Yueh Wu, Hua-Lin Jiang, Meei Jyh |
author_facet | Pai, Vincent Chunpeng Lo, I-Chung Huang, Yan wun Tsai, I-Ching Cheng, Hui-Pin Shi, Guey-Yueh Wu, Hua-Lin Jiang, Meei Jyh |
author_sort | Pai, Vincent Chunpeng |
collection | PubMed |
description | BACKGROUND: Thrombomodulin (TM), a transmembrane glycoprotein highly expressed in endothelial cells (ECs), is a potent anticoagulant maintaining circulation homeostasis. Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust expression of TM. The functional role of TM in VSMCs remains elusive. METHODS: We examined the role of TM in VSMCs activities in human aortic VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB). Using rat embryonic aorta-derived A7r5 VSMCs which do not express TM, the role of the chondroitin sulfate (CS) moiety of TM in VSMCs was delineated with cells expressing wild-type TM and the CS-devoid TM mutant. RESULTS: Expression of TM enhanced cell migration and adhesion/spreading onto type I collagen, but had no effect on cell proliferation. Knocking down TM with short hairpin RNA reduced PDGF-stimulated adhesion and migration of human aortic VSMCs. In A7r5 cells, TM-mediated cell adhesion was eradicated by pretreatment with chondroitinase ABC which degrades CS moiety. Furthermore, the TM mutant (TM(S490, 492A)) devoid of CS moiety failed to increase cell adhesion, spreading or migration. Wild-type TM, but not TM(S490, 492A), increased focal adhesion kinase (FAK) activation during cell adhesion, and TM-enhanced cell migration was abolished by a function-blocking anti-integrin β(1) antibody. CONCLUSION: Chondroitin sulfate modification is required for TM-mediated activation of β(1)-integrin and FAK, thereby enhancing adhesion and migration activity of VSMCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0415-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5809974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58099742018-02-16 The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells Pai, Vincent Chunpeng Lo, I-Chung Huang, Yan wun Tsai, I-Ching Cheng, Hui-Pin Shi, Guey-Yueh Wu, Hua-Lin Jiang, Meei Jyh J Biomed Sci Research BACKGROUND: Thrombomodulin (TM), a transmembrane glycoprotein highly expressed in endothelial cells (ECs), is a potent anticoagulant maintaining circulation homeostasis. Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust expression of TM. The functional role of TM in VSMCs remains elusive. METHODS: We examined the role of TM in VSMCs activities in human aortic VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB). Using rat embryonic aorta-derived A7r5 VSMCs which do not express TM, the role of the chondroitin sulfate (CS) moiety of TM in VSMCs was delineated with cells expressing wild-type TM and the CS-devoid TM mutant. RESULTS: Expression of TM enhanced cell migration and adhesion/spreading onto type I collagen, but had no effect on cell proliferation. Knocking down TM with short hairpin RNA reduced PDGF-stimulated adhesion and migration of human aortic VSMCs. In A7r5 cells, TM-mediated cell adhesion was eradicated by pretreatment with chondroitinase ABC which degrades CS moiety. Furthermore, the TM mutant (TM(S490, 492A)) devoid of CS moiety failed to increase cell adhesion, spreading or migration. Wild-type TM, but not TM(S490, 492A), increased focal adhesion kinase (FAK) activation during cell adhesion, and TM-enhanced cell migration was abolished by a function-blocking anti-integrin β(1) antibody. CONCLUSION: Chondroitin sulfate modification is required for TM-mediated activation of β(1)-integrin and FAK, thereby enhancing adhesion and migration activity of VSMCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0415-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-13 /pmc/articles/PMC5809974/ /pubmed/29439742 http://dx.doi.org/10.1186/s12929-018-0415-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Pai, Vincent Chunpeng Lo, I-Chung Huang, Yan wun Tsai, I-Ching Cheng, Hui-Pin Shi, Guey-Yueh Wu, Hua-Lin Jiang, Meei Jyh The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title | The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title_full | The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title_fullStr | The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title_full_unstemmed | The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title_short | The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
title_sort | chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809974/ https://www.ncbi.nlm.nih.gov/pubmed/29439742 http://dx.doi.org/10.1186/s12929-018-0415-7 |
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