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RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations
BACKGROUND: The blood flow rate of brain arteriovenous malformations (bAVMs) is an important clinical characteristic closely associated with the hemorrhage risk and radiosurgery obliteration rate of bAVMs. However, the underlying molecular properties remain unclear. To identify potential key molecul...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645621/ https://www.ncbi.nlm.nih.gov/pubmed/31170876 http://dx.doi.org/10.1161/JAHA.119.012746 |
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author | Huo, Ran Fu, Weilun Li, Hao Jiao, Yuming Yan, Zihan Wang, Linjian Wang, Jie Wang, Shuo Cao, Yong Zhao, Jizong |
author_facet | Huo, Ran Fu, Weilun Li, Hao Jiao, Yuming Yan, Zihan Wang, Linjian Wang, Jie Wang, Shuo Cao, Yong Zhao, Jizong |
author_sort | Huo, Ran |
collection | PubMed |
description | BACKGROUND: The blood flow rate of brain arteriovenous malformations (bAVMs) is an important clinical characteristic closely associated with the hemorrhage risk and radiosurgery obliteration rate of bAVMs. However, the underlying molecular properties remain unclear. To identify potential key molecules, signaling pathways, and vascular cell types involved, we compared gene expression profiles between bAVMs with high flow rates and low flow rates (LFR) and validated the functions of selected key molecules in vitro. METHODS AND RESULTS: We performed RNA‐sequencing analysis on 51 samples, including 14 high flow rate bAVMs and 37 LFR bAVMs. Functional pathway analysis was performed to identify potential signals influencing the flow rate phenotype of bAVMs. Candidate genes were investigated in bAVM specimens by immunohistochemical staining. Migration, tube formation, and proliferation assays were used to test the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells and human brain vascular smooth muscle cells. We identified 250 upregulated and 118 downregulated genes in LFR bAVMs compared with high flow rate bAVMs. Wnt signaling was activated in the LFR group via upregulation of FZD10 and MYOC. Immunohistochemical staining showed that vascular endothelial and smooth muscle cells of LFR bAVMs exhibited increased FZD10 and MYOC expression. Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in vitro. CONCLUSIONS: Our results suggest that canonical Wnt signaling mediated by FZD10 and MYOC is activated in vascular endothelial and smooth muscle cells in LFR bAVMs. |
format | Online Article Text |
id | pubmed-6645621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66456212019-07-31 RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations Huo, Ran Fu, Weilun Li, Hao Jiao, Yuming Yan, Zihan Wang, Linjian Wang, Jie Wang, Shuo Cao, Yong Zhao, Jizong J Am Heart Assoc Original Research BACKGROUND: The blood flow rate of brain arteriovenous malformations (bAVMs) is an important clinical characteristic closely associated with the hemorrhage risk and radiosurgery obliteration rate of bAVMs. However, the underlying molecular properties remain unclear. To identify potential key molecules, signaling pathways, and vascular cell types involved, we compared gene expression profiles between bAVMs with high flow rates and low flow rates (LFR) and validated the functions of selected key molecules in vitro. METHODS AND RESULTS: We performed RNA‐sequencing analysis on 51 samples, including 14 high flow rate bAVMs and 37 LFR bAVMs. Functional pathway analysis was performed to identify potential signals influencing the flow rate phenotype of bAVMs. Candidate genes were investigated in bAVM specimens by immunohistochemical staining. Migration, tube formation, and proliferation assays were used to test the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells and human brain vascular smooth muscle cells. We identified 250 upregulated and 118 downregulated genes in LFR bAVMs compared with high flow rate bAVMs. Wnt signaling was activated in the LFR group via upregulation of FZD10 and MYOC. Immunohistochemical staining showed that vascular endothelial and smooth muscle cells of LFR bAVMs exhibited increased FZD10 and MYOC expression. Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in vitro. CONCLUSIONS: Our results suggest that canonical Wnt signaling mediated by FZD10 and MYOC is activated in vascular endothelial and smooth muscle cells in LFR bAVMs. John Wiley and Sons Inc. 2019-06-07 /pmc/articles/PMC6645621/ /pubmed/31170876 http://dx.doi.org/10.1161/JAHA.119.012746 Text en © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Huo, Ran Fu, Weilun Li, Hao Jiao, Yuming Yan, Zihan Wang, Linjian Wang, Jie Wang, Shuo Cao, Yong Zhao, Jizong RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title |
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title_full |
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title_fullStr |
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title_full_unstemmed |
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title_short |
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations |
title_sort | rna sequencing reveals the activation of wnt signaling in low flow rate brain arteriovenous malformations |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645621/ https://www.ncbi.nlm.nih.gov/pubmed/31170876 http://dx.doi.org/10.1161/JAHA.119.012746 |
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