Yujing Zhao, Juan Wu, Shuai Guan, Ting Xue, Xiaolei Wei, Dawei Cao, Pengzhou Kong, Xinri Zhang
The First Hospital of Shanxi Medical University. The First People’s Hospital of Datong.
China
International Journal of Chronic Obstructive Pulmonary Disease
Int J Chron Obstruct Pulmon Dis 2023; 18: 1319-1332
DOI: 10.2147/COPD.S406453
Abstract
Purpose: Pulmonary artery hypertension (PAH) is a common complication of chronic obstructive pulmonary disease and obstructive sleep apnea/hypopnea syndrome worldwide. Pulmonary vascular alterations associated with PAH have multifactorial causes, in which endothelial cells play an important role. Autophagy is closely related to endothelial cell injury and the development of PAH. PIF1 is a multifunctional helicase crucial for cell survival. The present study investigated the effect of PIF1 on autophagy and apoptosis in human pulmonary artery endothelial cells (HPAECs) under chronic hypoxia stress.
Methods: Chronic hypoxia Gene expression profiling chip-assays identified the PIF1 gene as differentially expressed, which was verified by RT-qPCR analysis. Electron microscopy, immunofluorescence, and Western blotting were used to analyze autophagy and the expression of LC3 and P62. Apoptosis was analyzed using flow cytometry.
Results: Our study found that chronic hypoxia induces autophagy in HPAECs, and apoptosis was exacerbated by inhibiting autophagy. Levels of the DNA helicase PIF1 were increased in HPAECs after chronic hypoxia. PIF1 knockdown inhibited autophagy and promoted the apoptosis of HPAECs under chronic hypoxia stress.
Conclusion: Based on these findings, we conclude that PIF1 inhibits the apoptosis of HPAECs by accelerating the autophagy pathway. Therefore, PIF1 plays a crucial role in HPAEC dysfunction in chronic hypoxia-induced PAH and may be a potential target for the treatment of PAH.
Category
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes