The Role and Mechanism of HIF‐1α in Regulating A549 Alveolar Epithelial Cell Function Under Hypoxic Conditions

Objective This study aims to investigate the regulatory role and mechanism of hypoxia‐inducible transcription Factor 1 (HIF‐1α) in alveolar epithelial cell function under hypoxic conditions using A549 cells as a surrogate model. Methods Human A549 alveolar epithelial cells were used as the experimental model. HIF‐1α expression was modulated by siRNA knockdown or plasmid overexpression. qRT‐PCR quantified HIF‐1α, SP‐C, and vascular endothelial growth factor (VEGF) mRNA levels, and Western blotting evaluated the corresponding proteins and apoptosis‐related markers (cleaved Caspase 3, Bcl‐2, Bax). Cell counting kit 8 (CCK‐8) assessed A549 cell viability, while transwell assays measured migration (uncoated membrane) and invasion (Matrigel‐coated membrane). Terminal deoxynucleotidyl transferase–mediated dUTP nick‐end labeling (TUNEL) staining detected the apoptosis. Enzyme‐linked immunosorbent assay (ELISA) quantified VEGF secretion, and tube‐formation assays evaluated the proangiogenic effects of A549‐conditioned media on human umbilical vein endothelial cells (HUVECs). Results Hypoxia markedly increased HIF‐1α and VEGF expression while reducing SP‐C expression in A549 cells. HIF‐1α knockdown decreased VEGF expression and angiogenesis, restored cell viability, and suppressed migration, invasion, and apoptosis. In contrast, HIF‐1α overexpression further enhanced angiogenesis, promoted migration and invasion, and increased apoptosis. Conclusions HIF‐1α is a key regulator of hypoxia‐induced functional changes in alveolar epithelial cells, influencing cell viability, migration, invasion, apoptosis, VEGF production, and proangiogenic activity. These findings highlight their potential as a therapeutic target in hypoxia‐related lung injury.