Involvement of TFAP2A in the activation of GSDMD gene promoter in hyperoxia-induced ALI
| Autor: | Zhi-Dan Fan, Xiao-Qing Chen, Lan-Bo Zhou, Rui Jin, Dan-dan Feng, Guo-Ping Zhou, Yu-fei Chen, Jia He, Qian Cao |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Acute Lung Injury E2F4 Transcription Factor Lung injury Biology TFAP2A 03 medical and health sciences 0302 clinical medicine Intensive care Intensive Care Units Neonatal medicine Pyroptosis Animals Humans Promoter Regions Genetic E2F4 Hyperoxia Lung Intracellular Signaling Peptides and Proteins Promoter Cell Biology respiratory system Phosphate-Binding Proteins Cell Hypoxia respiratory tract diseases Cell biology Rats Oxygen 030104 developmental biology medicine.anatomical_structure Animals Newborn Gene Expression Regulation Transcription Factor AP-2 A549 Cells 030220 oncology & carcinogenesis medicine.symptom Transcription Initiation Site |
| Zdroj: | Experimental cell research. 401(1) |
| ISSN: | 1090-2422 |
| Popis: | Oxygen therapy is a common treatment in neonatal intensive care units, but long-term continuous hyperoxia ventilation may induce acute lung injury (ALI). Gasdermin D (GSDMD)-mediated pyroptosis participates in various diseases including ALI, but the role of GSDMD in hyperoxia-induced ALI is yet understood. Here, we showed a significant increase in GSDMD after exposure to high oxygen. To elucidate the molecular mechanisms involved in GSDMD regulation, we identified the core promoter of GSDMD, −98 ~ −12 bp relative to the transcriptional start site (TSS). The results of mutational analysis, overexpression or siRNA interference, EMSA and ChIP demonstrated that E2F4 and TFAP2A positively regulate the transcriptional activity of the GSDMD by binding to its promoter. However, only TFAP2A showed a regulatory effect on the expression of GSDMD. Moreover, TFAP2A was increased in the lung tissues of rats exposed to hyperoxia and showed a strong linear correlation with GSDMD. Our results indicated that TFAP2A positively regulates the GSDMD expression via binding to the promoter region of GSDMD. |
| Databáze: | OpenAIRE |
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