Expression of a Novel RNA-Splicing Factor, RA301/Tra2β, in Vascular Lesions and Its Role in Smooth Muscle Cell Proliferation

RA301/Tra2β, a sequence-specific RNA-binding protein, was first cloned as a stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have found enhanced RA301/Tra2β expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2β transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2β and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2β. Consistent with a link between RA301/Tra2β and cell proliferation, platelet-derived growth factor also induced expression of RA301/Tra2β in cultured VSMCs. These data suggest a possible role for RA301/Tra2β in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.