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Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke
Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urg...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710457/ https://www.ncbi.nlm.nih.gov/pubmed/34966392 http://dx.doi.org/10.3389/fimmu.2021.801985 |
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author | He, Qianyan Ma, Yinzhong Liu, Jie Zhang, Dianhui Ren, Jiaxin Zhao, Ruoyu Chang, JunLei Guo, Zhen-Ni Yang, Yi |
author_facet | He, Qianyan Ma, Yinzhong Liu, Jie Zhang, Dianhui Ren, Jiaxin Zhao, Ruoyu Chang, JunLei Guo, Zhen-Ni Yang, Yi |
author_sort | He, Qianyan |
collection | PubMed |
description | Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed. |
format | Online Article Text |
id | pubmed-8710457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87104572021-12-28 Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke He, Qianyan Ma, Yinzhong Liu, Jie Zhang, Dianhui Ren, Jiaxin Zhao, Ruoyu Chang, JunLei Guo, Zhen-Ni Yang, Yi Front Immunol Immunology Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed. Frontiers Media S.A. 2021-12-13 /pmc/articles/PMC8710457/ /pubmed/34966392 http://dx.doi.org/10.3389/fimmu.2021.801985 Text en Copyright © 2021 He, Ma, Liu, Zhang, Ren, Zhao, Chang, Guo and Yang https://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 | Immunology He, Qianyan Ma, Yinzhong Liu, Jie Zhang, Dianhui Ren, Jiaxin Zhao, Ruoyu Chang, JunLei Guo, Zhen-Ni Yang, Yi Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title | Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title_full | Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title_fullStr | Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title_full_unstemmed | Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title_short | Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke |
title_sort | biological functions and regulatory mechanisms of hypoxia-inducible factor-1α in ischemic stroke |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710457/ https://www.ncbi.nlm.nih.gov/pubmed/34966392 http://dx.doi.org/10.3389/fimmu.2021.801985 |
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