Oxygen-sensing mechanisms in development and tissue repair
Yida Jiang1, Li-Juan Duan1, Guo-Hua Fong1,2
1Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Development (Cambridge, England)
|December 7, 2021
Summary
Hypoxia-inducible factors (HIFs) regulate development by stabilizing under low oxygen, controlling gene expression. This primer explains the oxygen-sensing pathway, HIFs, and their role in development and disease.
Area of Science:
- Molecular Biology
- Developmental Biology
- Physiology
Background:
- Oxygen levels critically regulate cellular processes, including gene expression.
- Hypoxia-inducible factors (HIFs) are key mediators of the cellular response to oxygen.
- HIFα subunits are normally hydroxylated by prolyl hydroxylase domain proteins (PHDs) and degraded under normoxia.
Purpose of the Study:
- To elucidate the molecular mechanisms of the oxygen-sensing pathway.
- To summarize hypoxia-inducible factor (HIF)-regulated downstream events.
- To discuss loss-of-function phenotypes in mouse development and clinical relevance.
Main Methods:
- Review of molecular mechanisms governing oxygen sensing.
- Summary of known HIF-regulated genes and pathways.
- Analysis of developmental phenotypes in genetic models.
Main Results:
- Under hypoxia, PHD activity is suppressed, leading to HIFα stabilization.
- Stabilized HIFα regulates genes involved in angiogenesis, erythropoiesis, and metabolism.
- Loss-of-function studies reveal essential roles for HIF in embryonic development.
Conclusions:
- The oxygen-sensing pathway involving HIFs is crucial for normal embryogenesis.
- Dysregulation of HIF signaling is implicated in various diseases, including cancer and ischemic conditions.
- Understanding HIF biology offers therapeutic targets for angiogenesis and tissue repair.
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