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.