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ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype
ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539764/ https://www.ncbi.nlm.nih.gov/pubmed/34681953 http://dx.doi.org/10.3390/ijms222011293 |
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author | Sheldon, Helen Alexander, John Bridges, Esther Moreira, Lucia Reilly, Svetlana Ang, Koon Hwee Wang, Dian Lin, Salwa Haider, Syed Banham, Alison H. Harris, Adrian L. |
author_facet | Sheldon, Helen Alexander, John Bridges, Esther Moreira, Lucia Reilly, Svetlana Ang, Koon Hwee Wang, Dian Lin, Salwa Haider, Syed Banham, Alison H. Harris, Adrian L. |
author_sort | Sheldon, Helen |
collection | PubMed |
description | ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in endothelial-mesenchymal transistion (EndMT) with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes. |
format | Online Article Text |
id | pubmed-8539764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85397642021-10-24 ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype Sheldon, Helen Alexander, John Bridges, Esther Moreira, Lucia Reilly, Svetlana Ang, Koon Hwee Wang, Dian Lin, Salwa Haider, Syed Banham, Alison H. Harris, Adrian L. Int J Mol Sci Article ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in endothelial-mesenchymal transistion (EndMT) with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes. MDPI 2021-10-19 /pmc/articles/PMC8539764/ /pubmed/34681953 http://dx.doi.org/10.3390/ijms222011293 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sheldon, Helen Alexander, John Bridges, Esther Moreira, Lucia Reilly, Svetlana Ang, Koon Hwee Wang, Dian Lin, Salwa Haider, Syed Banham, Alison H. Harris, Adrian L. ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title | ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title_full | ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title_fullStr | ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title_full_unstemmed | ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title_short | ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype |
title_sort | eltd1 activation induces an endothelial-emt transition to a myofibroblast phenotype |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539764/ https://www.ncbi.nlm.nih.gov/pubmed/34681953 http://dx.doi.org/10.3390/ijms222011293 |
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