Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-01080-1 |
| _version_ | 1828427031042326528 |
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| author | Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu |
| author_facet | Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu |
| author_sort | Zhen Luo |
| collection | DOAJ |
| description | Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs. |
| first_indexed | 2024-12-10T16:55:20Z |
| format | Article |
| id | doaj.art-5687483c7a1f4a87897b306b98f3cc0e |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-10T16:55:20Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-5687483c7a1f4a87897b306b98f3cc0e2022-12-22T01:40:46ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-07-017113010.1038/s41392-022-01080-1Hypoxia signaling in human health and diseases: implications and prospects for therapeuticsZhen Luo0Mingfu Tian1Ge Yang2Qiaoru Tan3Yubing Chen4Geng Li5Qiwei Zhang6Yongkui Li7Pin Wan8Jianguo Wu9Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityFoshan Institute of Medical MicrobiologyFoshan Institute of Medical MicrobiologyThe Affiliated Shunde Hospital of Jinan UniversityGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityFoshan Institute of Medical MicrobiologyGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan UniversityAbstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.https://doi.org/10.1038/s41392-022-01080-1 |
| spellingShingle | Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu Hypoxia signaling in human health and diseases: implications and prospects for therapeutics Signal Transduction and Targeted Therapy |
| title | Hypoxia signaling in human health and diseases: implications and prospects for therapeutics |
| title_full | Hypoxia signaling in human health and diseases: implications and prospects for therapeutics |
| title_fullStr | Hypoxia signaling in human health and diseases: implications and prospects for therapeutics |
| title_full_unstemmed | Hypoxia signaling in human health and diseases: implications and prospects for therapeutics |
| title_short | Hypoxia signaling in human health and diseases: implications and prospects for therapeutics |
| title_sort | hypoxia signaling in human health and diseases implications and prospects for therapeutics |
| url | https://doi.org/10.1038/s41392-022-01080-1 |
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