2. Academic Validation
  3. Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

  • Signal Transduct Target Ther. 2022 Jul 7;7(1):218. doi: 10.1038/s41392-022-01080-1.
Zhen Luo # 1 2,  Mingfu Tian # 1 3,  Ge Yang # 2,  Qiaoru Tan 2,  Yubing Chen 4,  Geng Li 1 2,  Qiwei Zhang 1 2,  Yongkui Li 1 2,  Pin Wan 5,  Jianguo Wu 6 7 8
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, China.
  • 2 Foshan Institute of Medical Microbiology, Foshan, 528315, China.
  • 3 The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
  • 4 The Affiliated Shunde Hospital of Jinan University, Foshan, 528303, China.
  • 5 Foshan Institute of Medical Microbiology, Foshan, 528315, China. [email protected].
  • 6 Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, China. [email protected].
  • 7 Foshan Institute of Medical Microbiology, Foshan, 528315, China. [email protected].
  • 8 The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China. [email protected].
  • # Contributed equally.
PMID: 35798726 DOI: 10.1038/s41392-022-01080-1
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.

Figures