Hsieh C M, Yoshizumi M, Endege W O, Kho C J, Jain M K, Kashiki S, de los Santos R, Lee W S, Perrella M A, Lee M E
Department of Medicine, Harvard Medical School, Pulmonary and Cardiovascular Divisions, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Biol Chem. 1996 Jul 19;271(29):17354-9. doi: 10.1074/jbc.271.29.17354.
Despite the importance of phenotypic alterations in arterial smooth muscle cells (ASMC) during the pathogenesis of arteriosclerosis, little is known about genes that define differentiated ASMC. Using differential mRNA display, we isolated a novel gene preferentially expressed in the rat aorta and termed this gene APEG-1. The cDNA of rat APEG-1 contained an open reading frame encoding 113 amino acids, which would predict a basic protein of 12.7 kDa. The amino acid sequence of rat APEG-1 was highly conserved among human and mouse homologues (97 and 98%, respectively). Using an APEG-1 fusion protein containing an N-terminal c-Myc tag, we identified APEG-1 as a nuclear protein. By in situ hybridization, APEG-1 mRNA was expressed in rat ASMC. Although APEG-1 was expressed highly in differentiated ASMC in vivo, its expression was quickly down-regulated and disappeared in dedifferentiated ASMC in culture. In vivo, APEG-1 mRNA levels decreased by more than 80% in response to vascular injury as ASMC changed from a quiescent to a proliferative phenotype. Taken together, these data indicate that APEG-1 is a novel marker for differentiated ASMC and may have a role in regulating growth and differentiation of this cell type.
尽管动脉平滑肌细胞（ASMC）的表型改变在动脉粥样硬化发病机制中具有重要意义，但对于定义分化型ASMC的基因却知之甚少。利用差异mRNA显示技术，我们分离出一个在大鼠主动脉中优先表达的新基因，并将其命名为APEG-1。大鼠APEG-1的cDNA包含一个编码113个氨基酸的开放阅读框，预测其为一个12.7 kDa的碱性蛋白。大鼠APEG-1的氨基酸序列在人和小鼠同源物中高度保守（分别为97%和98%）。利用含有N端c-Myc标签的APEG-1融合蛋白，我们确定APEG-1为一种核蛋白。通过原位杂交，APEG-1 mRNA在大鼠ASMC中表达。虽然APEG-1在体内分化型ASMC中高表达，但其表达在培养的去分化ASMC中迅速下调并消失。在体内，随着ASMC从静止表型转变为增殖表型，血管损伤后APEG-1 mRNA水平下降超过80%。综上所述，这些数据表明APEG-1是分化型ASMC 的一种新型标志物，可能在调节这种细胞类型的生长和分化中发挥作用。
