PDF(Pubmed)
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：哮喘的复杂性，以气道炎症和重塑为标志，受缺氧条件的影响。本研究的重点是低氧诱导因子-1α（HIF-1α）和P53泛素化在哮喘加重中的作用。
方法：采用高通量测序和生物信息学方法鉴定与哮喘进展相关的基因，重点是GO和KEGG通路分析。建立了哮喘小鼠模型,分离气道平滑肌细胞(ASMCs),建立体外缺氧模型。细胞活力，扩散,迁移,并对细胞凋亡进行了评估，以及ELISA和苏木精和伊红(H&E)染色。
结果：在体内和体外哮喘模型中均观察到HIF-1α的显著增加。HIF-1α上调增强ASMC活力，扩散,和移民,在减少细胞凋亡的同时，主要通过MDM2促进P53泛素化。体内研究显示炎症细胞浸润增加，气道结构改变，通过抑制剂IDF-11,774缓解。
结论：该研究强调了HIF-1α-MDM2-P53轴在哮喘中的关键作用，表明其作为治疗干预目标的潜力。研究结果表明，调节该途径可以为治疗复杂的哮喘呼吸系统疾病提供新的途径。
方法：采用高通量测序和生物信息学方法鉴定与哮喘进展相关的基因，重点是GO和KEGG通路分析。建立了哮喘小鼠模型,分离气道平滑肌细胞(ASMCs),建立体外缺氧模型。细胞活力，扩散,迁移,并对细胞凋亡进行了评估，以及ELISA和苏木精和伊红(H&E)染色。
结果：在体内和体外哮喘模型中均观察到HIF-1α的显著增加。HIF-1α上调增强ASMC活力，扩散,和移民,在减少细胞凋亡的同时，主要通过MDM2促进P53泛素化。体内研究显示炎症细胞浸润增加，气道结构改变，通过抑制剂IDF-11,774缓解。
结论：该研究强调了HIF-1α-MDM2-P53轴在哮喘中的关键作用，表明其作为治疗干预目标的潜力。研究结果表明，调节该途径可以为治疗复杂的哮喘呼吸系统疾病提供新的途径。
