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A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation

Vascular endothelial growth factor (VEGF) plays a pivotal role in regulating cerebral angiogenesis after stroke. Meanwhile, excessive VEGF expression induces increased microvascular permeability in brain, probably leading to neurological deterioration. Therefore, the appropriate level of VEGF expres...

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Autores principales: Zhang, Song, Chen, Anqi, Chen, Xiaolu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010145/
https://www.ncbi.nlm.nih.gov/pubmed/33815136
http://dx.doi.org/10.3389/fphys.2021.619904
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author Zhang, Song
Chen, Anqi
Chen, Xiaolu
author_facet Zhang, Song
Chen, Anqi
Chen, Xiaolu
author_sort Zhang, Song
collection PubMed
description Vascular endothelial growth factor (VEGF) plays a pivotal role in regulating cerebral angiogenesis after stroke. Meanwhile, excessive VEGF expression induces increased microvascular permeability in brain, probably leading to neurological deterioration. Therefore, the appropriate level of VEGF expression is significant to the recovery of brain exposed to stroke. In this work, we demonstrate that microRNA-150 (miR-150) and its predicted target MYB form a negative feedback loop to control the level of post-stroke VEGF expression. Repression of MYB leads to decreased expression of miR-150 in brain microvascular endothelial cells (BMVECs) exposed to oxygen glucose deprivation (OGD), thus miR-150 was predicted to be down-regulated by MYB. Moreover, MYB was confirmed to be a direct target of miR-150 by using dual luciferase reporter assay. In our previous work, we have validated VEGF as another direct target of miR-150. Therefore, MYB participates in regulation of VEGF via miR-150 under OGD, forming a feedback loop with miR-150. We also find that high levels of miR-150 inhibitors combined with MYB silence contribute to further enhancement of VEGF expression in BMVECs in response to OGD. These observations suggest that the feedback loop comprised of miR-150 and MYB, which is a pivotal endogenous epigenetic regulation to control the expression levels of VEGF in BMVECs subjected to OGD.
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spelling pubmed-80101452021-04-01 A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation Zhang, Song Chen, Anqi Chen, Xiaolu Front Physiol Physiology Vascular endothelial growth factor (VEGF) plays a pivotal role in regulating cerebral angiogenesis after stroke. Meanwhile, excessive VEGF expression induces increased microvascular permeability in brain, probably leading to neurological deterioration. Therefore, the appropriate level of VEGF expression is significant to the recovery of brain exposed to stroke. In this work, we demonstrate that microRNA-150 (miR-150) and its predicted target MYB form a negative feedback loop to control the level of post-stroke VEGF expression. Repression of MYB leads to decreased expression of miR-150 in brain microvascular endothelial cells (BMVECs) exposed to oxygen glucose deprivation (OGD), thus miR-150 was predicted to be down-regulated by MYB. Moreover, MYB was confirmed to be a direct target of miR-150 by using dual luciferase reporter assay. In our previous work, we have validated VEGF as another direct target of miR-150. Therefore, MYB participates in regulation of VEGF via miR-150 under OGD, forming a feedback loop with miR-150. We also find that high levels of miR-150 inhibitors combined with MYB silence contribute to further enhancement of VEGF expression in BMVECs in response to OGD. These observations suggest that the feedback loop comprised of miR-150 and MYB, which is a pivotal endogenous epigenetic regulation to control the expression levels of VEGF in BMVECs subjected to OGD. Frontiers Media S.A. 2021-03-17 /pmc/articles/PMC8010145/ /pubmed/33815136 http://dx.doi.org/10.3389/fphys.2021.619904 Text en Copyright © 2021 Zhang, Chen and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Zhang, Song
Chen, Anqi
Chen, Xiaolu
A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title_full A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title_fullStr A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title_full_unstemmed A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title_short A Feedback Loop Involving MicroRNA-150 and MYB Regulates VEGF Expression in Brain Microvascular Endothelial Cells After Oxygen Glucose Deprivation
title_sort feedback loop involving microrna-150 and myb regulates vegf expression in brain microvascular endothelial cells after oxygen glucose deprivation
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010145/
https://www.ncbi.nlm.nih.gov/pubmed/33815136
http://dx.doi.org/10.3389/fphys.2021.619904
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