Tsukamoto Y, Matsuo N, Ozawa K, Hori O, Higashi T, Nishizaki J, Tohnai N, Nagata I, Kawano K, Yutani C, Hirota S, Kitamura Y, Stern D M, Ogawa S
Department of Pathology and Neurosurgery, National Cardiovascular Center, Suita City, Japan.
Am J Pathol. 2001 May;158(5):1685-94. doi: 10.1016/s0002-9440(10)64124-7.
RA301/Tra2beta, 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/Tra2beta expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2beta 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/Tra2beta 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/Tra2beta. Consistent with a link between RA301/Tra2beta and cell proliferation, platelet-derived growth factor also induced expression of RA301/Tra2beta in cultured VSMCS: These data suggest a possible role for RA301/Tra2beta in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.
RA301/Tra2beta是一种序列特异性RNA结合蛋白，最初作为再充氧星形胶质细胞中的应激分子被克隆出来。在人体血管组织中，我们发现在内膜增厚的冠状动脉和动脉粥样硬化主动脉中RA301/Tra2beta表达增强。对大鼠颈动脉进行球囊损伤可诱导RA301/Tra2beta转录本产生，随后抗原表达，在内膜和新内膜血管平滑肌细胞（VSMC）中可检测到该抗原。在培养的VSMC中，缺氧/再充氧导致RA301/Tra2beta的诱导，并伴有细胞增殖，这两者均可通过添加二苯基碘鎓（一种NADPH氧化酶抑制剂）、PD98059（一种丝裂原活化蛋白激酶激酶抑制剂）或针对RA301/Tra2beta的反义寡核苷酸来阻断。与RA301/Tra2beta和细胞增殖之间的联系一致，血小板衍生生长因子也可在培养的VSMC中诱导RA301/Tra2beta的表达：这些数据表明RA301/Tra2beta在VSMC增殖调节中可能发挥作用，尤其是在缺氧/再充氧诱导的细胞应激情况下。
