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miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4

BACKGROUND: In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Mor...

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Autores principales: He, Ling, Yuan, Jing, Xu, Qingyun, Chen, Ruixue, Chen, Liguo, Fang, Meixia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990291/
https://www.ncbi.nlm.nih.gov/pubmed/27537404
http://dx.doi.org/10.1371/journal.pone.0159171
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author He, Ling
Yuan, Jing
Xu, Qingyun
Chen, Ruixue
Chen, Liguo
Fang, Meixia
author_facet He, Ling
Yuan, Jing
Xu, Qingyun
Chen, Ruixue
Chen, Liguo
Fang, Meixia
author_sort He, Ling
collection PubMed
description BACKGROUND: In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups. These results were confirmed using gene prediction software, which showed synergistic effects between ATF4 and miR-1283. ATF4 is a key molecule in ERS. Three ERS pathways exist:protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme-1 (IRE-1)-induced apoptosis. The PERK pathway is the most important and also includes the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and ATF4. In this report, we studied the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway using human umbilical vein endothelial cells (HUVECs) and mice. METHODOLOGY/PRINCIPAL FINDINGS: We verified the relationship between miR-1283 and ATF4 using a luciferase activity assay and observed the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: ATF4 is a target gene of miR-1283, which regulates the PERK-eIF2α-ATF4 signaling pathway by inhibiting ATF4, and it plays a critical role in inducing injury in HUVECs and mouse heart tissue.
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spelling pubmed-49902912016-08-29 miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4 He, Ling Yuan, Jing Xu, Qingyun Chen, Ruixue Chen, Liguo Fang, Meixia PLoS One Research Article BACKGROUND: In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups. These results were confirmed using gene prediction software, which showed synergistic effects between ATF4 and miR-1283. ATF4 is a key molecule in ERS. Three ERS pathways exist:protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme-1 (IRE-1)-induced apoptosis. The PERK pathway is the most important and also includes the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and ATF4. In this report, we studied the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway using human umbilical vein endothelial cells (HUVECs) and mice. METHODOLOGY/PRINCIPAL FINDINGS: We verified the relationship between miR-1283 and ATF4 using a luciferase activity assay and observed the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: ATF4 is a target gene of miR-1283, which regulates the PERK-eIF2α-ATF4 signaling pathway by inhibiting ATF4, and it plays a critical role in inducing injury in HUVECs and mouse heart tissue. Public Library of Science 2016-08-18 /pmc/articles/PMC4990291/ /pubmed/27537404 http://dx.doi.org/10.1371/journal.pone.0159171 Text en © 2016 He et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
He, Ling
Yuan, Jing
Xu, Qingyun
Chen, Ruixue
Chen, Liguo
Fang, Meixia
miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title_full miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title_fullStr miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title_full_unstemmed miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title_short miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4
title_sort mirna-1283 regulates the perk/atf4 pathway in vascular injury by targeting atf4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990291/
https://www.ncbi.nlm.nih.gov/pubmed/27537404
http://dx.doi.org/10.1371/journal.pone.0159171
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