Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1α in hypoxic pulmonary hypertension.

Pulmonary hypertension (PH) develops in 30-70% of chronic obstructive pulmonary disease patients and increases morbidity and mortality. The present study aimed to investigate the regulation of small ubiquitin‑related modifier‑1 (SUMO‑1) expression in response to hypoxia. The experiments were carried out in vitro in rat pulmonary arterial smooth muscle cells (PASMCs) and in vivo using a rat hypoxic PH (HPH) model. A significant increase in SUMO‑1 mRNA and protein levels was observed following hypoxic stimulation in vivo and in vitro. SUMO‑1 is known to interact with various transcription factors, including hypoxia‑inducible factor‑1α (HIF‑1α) in vitro. Notably, the expression of HIF‑1α and its target gene, vascular endothelial growth factor, was increased by hypoxia in HPH. In addition, the present data suggest that SUMO‑1 regulated HIF‑1α in response to hypoxia (gene silencing and overexpression). Finally, the co‑immunoprecipitation assays suggest a direct and specific interaction between SUMO‑1 and HIF‑1α. In conclusion, SUMO‑1 may participate in the modulation of HIF‑1α through sumoylation in HPH. However, further studies are required to confirm this.