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In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac...

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Autores principales: Bax, Noortje A. M., van Oorschot, Angelique A. M., Maas, Saskia, Braun, Jerry, van Tuyn, John, de Vries, Antoine A. F., Groot, Adriana C. Gittenberger-de, Goumans, Marie-José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149675/
https://www.ncbi.nlm.nih.gov/pubmed/21516490
http://dx.doi.org/10.1007/s00395-011-0181-0
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author Bax, Noortje A. M.
van Oorschot, Angelique A. M.
Maas, Saskia
Braun, Jerry
van Tuyn, John
de Vries, Antoine A. F.
Groot, Adriana C. Gittenberger-de
Goumans, Marie-José
author_facet Bax, Noortje A. M.
van Oorschot, Angelique A. M.
Maas, Saskia
Braun, Jerry
van Tuyn, John
de Vries, Antoine A. F.
Groot, Adriana C. Gittenberger-de
Goumans, Marie-José
author_sort Bax, Noortje A. M.
collection PubMed
description Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-011-0181-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-31496752011-09-08 In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1 Bax, Noortje A. M. van Oorschot, Angelique A. M. Maas, Saskia Braun, Jerry van Tuyn, John de Vries, Antoine A. F. Groot, Adriana C. Gittenberger-de Goumans, Marie-José Basic Res Cardiol Original Contribution Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-011-0181-0) contains supplementary material, which is available to authorized users. Springer-Verlag 2011-04-24 2011 /pmc/articles/PMC3149675/ /pubmed/21516490 http://dx.doi.org/10.1007/s00395-011-0181-0 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Contribution
Bax, Noortje A. M.
van Oorschot, Angelique A. M.
Maas, Saskia
Braun, Jerry
van Tuyn, John
de Vries, Antoine A. F.
Groot, Adriana C. Gittenberger-de
Goumans, Marie-José
In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title_full In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title_fullStr In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title_full_unstemmed In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title_short In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1
title_sort in vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by tgfβ-signaling and wt1
topic Original Contribution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149675/
https://www.ncbi.nlm.nih.gov/pubmed/21516490
http://dx.doi.org/10.1007/s00395-011-0181-0
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