1. Novel hypoxia-induced HIF-1αactivation in asthma pathogenesis.
- Author
-
Wan M, Yu Q, Xu F, You LX, Liang X, Kang Ren K, and Zhou J
- Subjects
- Animals, Mice, Cells, Cultured, Mice, Inbred BALB C, Apoptosis physiology, Cell Proliferation physiology, Proto-Oncogene Proteins c-mdm2 metabolism, Proto-Oncogene Proteins c-mdm2 genetics, Hypoxia metabolism, Hypoxia pathology, Disease Models, Animal, Cell Hypoxia physiology, Female, Humans, Cell Movement physiology, Ubiquitination, Asthma metabolism, Asthma pathology, Asthma genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology
- Abstract
Background: Asthma's complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation., Methods: High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining., Results: A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs' viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774., Conclusion: The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF