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Nrf2 protects against airway disorders.
Hye-Youn Cho1, Steven R Kleeberger
1Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Building 101, MD D-201, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. cho2@niehs.nih.gov
Toxicology and Applied Pharmacology
|August 4, 2009
Summary
Nuclear factor-erythroid 2 related factor 2 (Nrf2) protects against lung injury by regulating antioxidant genes. Its absence worsens lung damage from various insults, highlighting Nrf2
Area of Science:
- Molecular Biology
- Cell Biology
- Toxicology
Background:
- Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a key transcription factor regulating antioxidant and cytoprotective genes.
- Kelch-like ECH-associated protein 1 (Keap1) normally inhibits Nrf2 activity and promotes its degradation.
- Nrf2 activation by various stimuli initiates cellular defense mechanisms against oxidative stress, inflammation, and carcinogenesis.
Purpose of the Study:
- To review the critical role of Nrf2 in protecting the airways against oxidative stress and injury.
- To summarize evidence from experimental models and human studies on Nrf2's function in lung health and disease.
Main Methods:
- Review of experimental studies using Nrf2 germ-line mutant mice to assess Nrf2's protective roles in various organs, including the lung.
- Analysis of microarray and bioinformatic data to identify Nrf2-regulated genes and signaling pathways involved in pulmonary protection.
- Examination of human genetic and epigenetic studies linking NRF2 and KEAP1 alterations to lung diseases.
Main Results:
- Nrf2 deficiency exacerbates lung injury induced by hyperoxia, cigarette smoke, allergens, viruses, endotoxins, environmental pollutants, and bleomycin.
- Nrf2 activation triggers cellular rescue pathways crucial for combating oxidative damage and inflammation in the lungs.
- Genetic alterations in NRF2 and KEAP1 are associated with human lung diseases like acute lung injury and lung cancer.
Conclusions:
- Nrf2 plays a vital protective role in the airways, mitigating damage from diverse oxidative and inflammatory insults.
- Dysregulation of the Nrf2-Keap1 pathway contributes to the pathogenesis of lung diseases.
- Targeting the Nrf2 pathway holds therapeutic potential for preventing and treating lung disorders.
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