Expression of a novel RNA-splicing factor, RA301/Tra2 beta, in vascular lesions and its role in smooth muscle cell proliferation

RA301/Tra2 beta, 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/Tra2 beta expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat c arotid artery induced RA301/Tra2 beta transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth m uscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induc tion of RA301/Tra2 beta and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxi dase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibito r, or antisense oligonucleotide for RA301/Tra2 beta, Consistent with a link between RA301/Tra2 beta and cell proliferation, platelet-derived growth fa ctor also induced expression of RA301/Tra2 beta in cultured VSMCs. These da ta suggest a possible role for RA301/Tra2 beta in the regulation of VSMC pr oliferation, especially in the setting of hypoxia/reoxygenation-induced cel l stress.