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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.801985/full |
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| author | Qianyan He Yinzhong Ma Jie Liu Dianhui Zhang Jiaxin Ren Ruoyu Zhao JunLei Chang Zhen-Ni Guo Yi Yang |
| author_facet | Qianyan He Yinzhong Ma Jie Liu Dianhui Zhang Jiaxin Ren Ruoyu Zhao JunLei Chang Zhen-Ni Guo Yi Yang |
| author_sort | Qianyan He |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T04:35:11Z |
| format | Article |
| id | doaj.art-f81c14632a6344df9ce5eeefc82af40d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T04:35:11Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f81c14632a6344df9ce5eeefc82af40d2022-12-21T23:17:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.801985801985Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic StrokeQianyan He0Yinzhong Ma1Jie Liu2Dianhui Zhang3Jiaxin Ren4Ruoyu Zhao5JunLei Chang6Zhen-Ni Guo7Yi Yang8Department of Neurology, The First Hospital of Jilin University, Changchun, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaShenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaIschemic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.801985/fullHIF-1αischemic strokehypoxianeurovascular unitneuroprotectionneuroinflammation |
| spellingShingle | Qianyan He Yinzhong Ma Jie Liu Dianhui Zhang Jiaxin Ren Ruoyu Zhao JunLei Chang Zhen-Ni Guo Yi Yang Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke Frontiers in Immunology HIF-1α ischemic stroke hypoxia neurovascular unit neuroprotection neuroinflammation |
| 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 | HIF-1α ischemic stroke hypoxia neurovascular unit neuroprotection neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.801985/full |
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