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Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular endothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further investigate the role of Rho/MRTF-A in angiogenesis b...

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Autores principales: Zhang, Rui, Wang, Nan, Zhang, Man, Zhang, Li-Nan, Guo, Zhi-Xia, Luo, Xue-Gang, Zhou, Hao, He, Hong-Peng, Zhang, Tong-Cun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408638/
https://www.ncbi.nlm.nih.gov/pubmed/25949242
http://dx.doi.org/10.1155/2015/534758
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author Zhang, Rui
Wang, Nan
Zhang, Man
Zhang, Li-Nan
Guo, Zhi-Xia
Luo, Xue-Gang
Zhou, Hao
He, Hong-Peng
Zhang, Tong-Cun
author_facet Zhang, Rui
Wang, Nan
Zhang, Man
Zhang, Li-Nan
Guo, Zhi-Xia
Luo, Xue-Gang
Zhou, Hao
He, Hong-Peng
Zhang, Tong-Cun
author_sort Zhang, Rui
collection PubMed
description Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular endothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further investigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression of integrins α1β1 and α5β1, which are known to mediate physiological and pathological angiogenesis. Our results showed that increased expression of α1, α5, and β1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling pathway was demonstrated to be involved in regulating the expression of integrins α1, α5, and β1. Luciferase reporter assay and ChIP assay determined that MRTF-A could bind to and transactivate the integrin α1 and α5 promoters. Treatment with the Rho inhibitor C3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation of α1, α5, and β1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion led to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate that Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic processes.
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spelling pubmed-44086382015-05-06 Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells Zhang, Rui Wang, Nan Zhang, Man Zhang, Li-Nan Guo, Zhi-Xia Luo, Xue-Gang Zhou, Hao He, Hong-Peng Zhang, Tong-Cun Stem Cells Int Research Article Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular endothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further investigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression of integrins α1β1 and α5β1, which are known to mediate physiological and pathological angiogenesis. Our results showed that increased expression of α1, α5, and β1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling pathway was demonstrated to be involved in regulating the expression of integrins α1, α5, and β1. Luciferase reporter assay and ChIP assay determined that MRTF-A could bind to and transactivate the integrin α1 and α5 promoters. Treatment with the Rho inhibitor C3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation of α1, α5, and β1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion led to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate that Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic processes. Hindawi Publishing Corporation 2015 2015-04-08 /pmc/articles/PMC4408638/ /pubmed/25949242 http://dx.doi.org/10.1155/2015/534758 Text en Copyright © 2015 Rui Zhang et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Zhang, Rui
Wang, Nan
Zhang, Man
Zhang, Li-Nan
Guo, Zhi-Xia
Luo, Xue-Gang
Zhou, Hao
He, Hong-Peng
Zhang, Tong-Cun
Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title_full Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title_fullStr Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title_full_unstemmed Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title_short Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells
title_sort rho/mrtf-a-induced integrin expression regulates angiogenesis in differentiated multipotent mesenchymal stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408638/
https://www.ncbi.nlm.nih.gov/pubmed/25949242
http://dx.doi.org/10.1155/2015/534758
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