Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype

Helen Sheldon
* ORCID logo ,
John Alexander
,
Esther M. Bridges
,
Lucia Moreira
,
Svetlana Reilly
,
Koon Hwee Ang
,
Dian Wang
,
Salwa Lin
,
Syed Haider
ORCID logo ,
Alison H. Banham
,
Adrian L. Harris
* ORCID logo
Version 1 : Received: 8 September 2021 / Approved: 23 September 2021 / Online: 23 September 2021 (11:34:28 CEST)

A peer-reviewed article of this Preprint also exists.

Sheldon, H.; Alexander, J.; Bridges, E.; Moreira, L.; Reilly, S.; Ang, K.H.; Wang, D.; Lin, S.; Haider, S.; Banham, A.H.; Harris, A.L. ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype. Int. J. Mol. Sci. 2021, 22, 11293. Sheldon, H.; Alexander, J.; Bridges, E.; Moreira, L.; Reilly, S.; Ang, K.H.; Wang, D.; Lin, S.; Haider, S.; Banham, A.H.; Harris, A.L. ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype. Int. J. Mol. Sci. 2021, 22, 11293.

Abstract

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 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.

Keywords

ELTD1; EMT; pro-angiogenic; myofibroblast

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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