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| Status |
Public on Oct 09, 2024 |
| Title |
GETomics based bulk-RNA sequencing revealed HIF-3α prevents COPD by inhibiting alveolar epithelial cell ferroptosis via the HIF-3α-GPx4 axis. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
COPD patients are largely asymptomatic until later stages when prognosis is generally poor. Here, by shifting the focus forward to pre-COPD and smoking stages, we found the peak of reactive oxygen species (ROS) level and hypoxia character are enriched in pre-COPD samples, and hypoxia inducible factor (HIF)-3α is the key factor. Smoking induced regional tissue hypoxia and emphysema have been found in COPD patients. However, the mechanisms underlying hypoxia especially HIF-3α and COPD have not been investigated. In this study, by leveraging scRNA-seq and EpCAM co-localization analysis we identified HIF-3α is downregulated in alveolar epithelial cells in COPD. In vitro experiments using lentivirus transfection, bulk-RNA seq and RSL3 we found the activation of HIF-3α-GPx4 axis inhibits alveolar epithelial cell ferroptosis under the treatment of cigarettes smoking extracts (CSE). Further results from SftpcCreert2/+R26LSL-Hif3a knock-in mice demonstrated overexpression of HIF-3α inhibits alveolar epithelial cells ferroptosis and prevents the declining of lung function. Our data suggest the activation of HIF-3α-GPx4 axis prevents COPD by inhibiting alveolar epithelial cells ferroptosis. By leveraging this comprehensive analysis method, more promising treatment targets will be found and enhance our understanding to the pathogenesis.
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| Overall design |
To explore the decades long COPD pathogenesis process by including non-smokers, smokers, pre-COPD and COPD patients.Using transcriptomics technology to delineate the changing chracter.
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| Contributor(s) |
Jiang J, Yang T, Wang C |
| Citation(s) |
39310101 |
| |
| Submission date |
Aug 22, 2024 |
| Last update date |
Oct 09, 2024 |
| Contact name |
Junchao Jiang |
| E-mail(s) |
[email protected]
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| Organization name |
Peking Union Medical College
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| Street address |
Dongdan Santiao, Doncheng District
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| City |
Beijing |
| ZIP/Postal code |
100000 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA1151128 |
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