Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1 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-1 (HIF-1) in vitro. Notably, the expression of HIF-1 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-1 in response to hypoxia (gene silencing and overexpression). Finally, the co-immunoprecipitation assays suggest a direct and specific interaction between SUMO-1 and HIF-1. In conclusion, SUMO-1 may participate in the modulation of HIF-1 through sumoylation in HPH. However, further studies are required to confirm this.