International Journal of COPD (Jun 2023)

PIF1 Promotes Autophagy to Inhibit Chronic Hypoxia Induced Apoptosis of Pulmonary Artery Endothelial Cells

  • Zhao Y,
  • Wu J,
  • Guan S,
  • Xue T,
  • Wei X,
  • Cao D,
  • Kong P,
  • Zhang X

Journal volume & issue
Vol. Volume 18
pp. 1319 – 1332

Abstract

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Yujing Zhao,1– 4 Juan Wu,2– 4 Shuai Guan,5 Ting Xue,2– 4 Xiaolei Wei,1– 4 Dawei Cao,2– 4 Pengzhou Kong,6 Xinri Zhang2– 4 1Department of the First Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of NHC Key Laboratory of Pneumoconiosis, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Shanxi Key Laboratory of Respiratory Diseases, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 5Department of Pediatric Infectious Diseases, The First People’s Hospital of Datong, Datong, Shanxi, People’s Republic of China; 6Department of Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Pengzhou Kong, Department of Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China, Email [email protected] Xinri Zhang, Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Pneumoconiosis; Shanxi Key Laboratory of Respiratory Diseases, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China, Email [email protected]: 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.Keywords: PIF1, autophagy, HPAEC, PAH, chronic hypoxia

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