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Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition
The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in disea...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387078/ https://www.ncbi.nlm.nih.gov/pubmed/30678183 http://dx.doi.org/10.3390/ijms20030458 |
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author | Ursoli Ferreira, Fernanda Eduardo Botelho Souza, Lucas Hassibe Thomé, Carolina Tomazini Pinto, Mariana Origassa, Clarice Salustiano, Suellen Marcel Faça, Vitor Olsen Câmara, Niels Kashima, Simone Tadeu Covas, Dimas |
author_facet | Ursoli Ferreira, Fernanda Eduardo Botelho Souza, Lucas Hassibe Thomé, Carolina Tomazini Pinto, Mariana Origassa, Clarice Salustiano, Suellen Marcel Faça, Vitor Olsen Câmara, Niels Kashima, Simone Tadeu Covas, Dimas |
author_sort | Ursoli Ferreira, Fernanda |
collection | PubMed |
description | The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor β (TGF-β) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-β2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs; primary aortic endothelial cells PAECs; human umbilical vein endothelia cells, HUVECs; and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal–regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation. |
format | Online Article Text |
id | pubmed-6387078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63870782019-02-27 Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition Ursoli Ferreira, Fernanda Eduardo Botelho Souza, Lucas Hassibe Thomé, Carolina Tomazini Pinto, Mariana Origassa, Clarice Salustiano, Suellen Marcel Faça, Vitor Olsen Câmara, Niels Kashima, Simone Tadeu Covas, Dimas Int J Mol Sci Article The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor β (TGF-β) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-β2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs; primary aortic endothelial cells PAECs; human umbilical vein endothelia cells, HUVECs; and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal–regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation. MDPI 2019-01-22 /pmc/articles/PMC6387078/ /pubmed/30678183 http://dx.doi.org/10.3390/ijms20030458 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ursoli Ferreira, Fernanda Eduardo Botelho Souza, Lucas Hassibe Thomé, Carolina Tomazini Pinto, Mariana Origassa, Clarice Salustiano, Suellen Marcel Faça, Vitor Olsen Câmara, Niels Kashima, Simone Tadeu Covas, Dimas Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title | Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title_full | Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title_fullStr | Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title_full_unstemmed | Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title_short | Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition |
title_sort | endothelial cells tissue-specific origins affects their responsiveness to tgf-β2 during endothelial-to-mesenchymal transition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387078/ https://www.ncbi.nlm.nih.gov/pubmed/30678183 http://dx.doi.org/10.3390/ijms20030458 |
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