Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784588826027491328
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
work_keys_str_mv AT sheldonhelen eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT alexanderjohn eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT bridgesesther eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT moreiralucia eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT reillysvetlana eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT angkoonhwee eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT wangdian eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT linsalwa eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT haidersyed eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT banhamalisonh eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype
AT harrisadrianl eltd1activationinducesanendothelialemttransitiontoamyofibroblastphenotype