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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2011
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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. |
format | Online Article Text |
id | pubmed-3149675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
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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