FP Prostanoid Receptor Mediated Up‐regulation of Hypoxia‐Inducible Factor‐1α through Activation of Mitogen‐Activated Protein Kinase and Reactive Oxygen Species Signaling Pathways

Abstract

The FP prostanoid receptor is in the family of G‐protein‐coupled receptors and is known to activate calcium and inositol phosphate signaling via coupling to Gq . It's complementary ligand is prostaglandin‐F2α (PGF2α). In human embryonic kidney (HEK) cells expressing the human FP receptor, we show that PGF2α stimulation of the FP receptor upregulates the expression of hypoxia‐inducible factor‐1α (HIF‐1α), under normoxic conditions, by activation of the mitogen activated protein kinase (MAPK) and reactive oxygen species (ROS) signaling pathways. Co‐expression of dominant negative Nurr1 (DN‐Nurr1) diminished the PGF2α stimulated upegulation of HIF‐1α expression. HIF‐1α is widely characterized in the literature as a tumor growth promoter and is often up‐regulated in cancer. Our findings provide a potential mechanism by which PGF2α could‐upregulate the expression of HIF‐1α through Nurr1 activation.