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The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition

Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we chara...

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Autores principales: Sobierajska, Katarzyna, Ciszewski, Wojciech M., Macierzynska-Piotrowska, Ewa, Klopocka, Wanda, Przygodzka, Patrycja, Karakula, Magdalena, Pestka, Karolina, Wawro, Marta E., Niewiarowska, Jolanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461591/
https://www.ncbi.nlm.nih.gov/pubmed/32824297
http://dx.doi.org/10.3390/ijms21165875
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author Sobierajska, Katarzyna
Ciszewski, Wojciech M.
Macierzynska-Piotrowska, Ewa
Klopocka, Wanda
Przygodzka, Patrycja
Karakula, Magdalena
Pestka, Karolina
Wawro, Marta E.
Niewiarowska, Jolanta
author_facet Sobierajska, Katarzyna
Ciszewski, Wojciech M.
Macierzynska-Piotrowska, Ewa
Klopocka, Wanda
Przygodzka, Patrycja
Karakula, Magdalena
Pestka, Karolina
Wawro, Marta E.
Niewiarowska, Jolanta
author_sort Sobierajska, Katarzyna
collection PubMed
description Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter’s regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process.
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spelling pubmed-74615912020-09-04 The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition Sobierajska, Katarzyna Ciszewski, Wojciech M. Macierzynska-Piotrowska, Ewa Klopocka, Wanda Przygodzka, Patrycja Karakula, Magdalena Pestka, Karolina Wawro, Marta E. Niewiarowska, Jolanta Int J Mol Sci Article Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter’s regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process. MDPI 2020-08-16 /pmc/articles/PMC7461591/ /pubmed/32824297 http://dx.doi.org/10.3390/ijms21165875 Text en © 2020 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
Sobierajska, Katarzyna
Ciszewski, Wojciech M.
Macierzynska-Piotrowska, Ewa
Klopocka, Wanda
Przygodzka, Patrycja
Karakula, Magdalena
Pestka, Karolina
Wawro, Marta E.
Niewiarowska, Jolanta
The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title_full The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title_fullStr The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title_full_unstemmed The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title_short The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition
title_sort new model of snail expression regulation: the role of mrtfs in fast and slow endothelial–mesenchymal transition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461591/
https://www.ncbi.nlm.nih.gov/pubmed/32824297
http://dx.doi.org/10.3390/ijms21165875
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