The nuclear receptor NOR-1 regulates vitronectin in human vascular smooth muscle cells

What is it about?

The nuclear receptor NOR-1 (NR4A3) plays a role in vascular remodelling and has recently been involved in the regulation of extracellular matrix (ECM) proteins associated to neointimal thickening and the vascular control of haemostasis. However, the information on NOR-1 target genes in the vasculature is still limited. Over-expression of NOR-1 strongly increased vitronectin mRNA and protein levels, while NOR-1 inhibition significantly reduced vitronectin expression. Vitronectin is a glycoprotein present in plasma, platelets and ECM that plays a major role in cell adhesion, migration/proliferation, thrombosis and fibrinolysis. An in silico analysis identified putative NOR-1 response elements in the proximal promoter region of vitronectin. Deletion and site-directed mutagenesis studies, as well as EMSA and ChIP identified the NBRE-202/-195 site in vitronectin promoter as an essential element for NOR-1 responsiveness. NOR-1 and vitronectin colocalized in VSMC in human atherosclerotic lesions suggesting a pathophysiological link between them. Using gain- and loss-of-function approaches we show NOR-1-mediated vitronectin secretion drives VSMC migration.

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Why is it important?

These results indicate that vitronectin is a new target of NOR-1 and suggest that this multifunctional glycoprotein may participate in vascular responses mediated by this nuclear receptor.

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