Kurita Souichi, Takeuchi Keisuke, Hayashi Yoshimi, Ueyama Hisao, Zankov Dimitar P, Pang Xiaoling, Otsuka Takanobu, Ohkubo Iwao, Ogikubo Osamu, Ogita Hisakazu
Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
Department of Orthopedic Surgery, Nagoya City University, Nagoya, Japan.
Hypertens Res. 2015 Apr;38(4):244-51. doi: 10.1038/hr.2014.165. Epub 2014 Nov 27.
Zn-α2-glycoprotein (ZAG) (molecular weight=41 kDa) is one component in the α2 fraction of human plasma, and is reported to be associated with several diseases, such as cancers and metabolic syndromes. ZAG is also considered to be an important modulator of lipid metabolism. However, little is known about the correlation of serum ZAG levels with indicators of metabolic syndrome. Serum ZAG concentrations analyzed by enzyme-linked immunoassay were positively correlated with systolic and diastolic blood pressure in 326 subjects (236 males and 90 females) aged 17-79 years who had an annual health examination. By luciferase reporter and electrophoretic mobility shift assays, the core promoter region to regulate the ZAG gene expression was found to exist between -110 and -101. The transcription factor Sp1 interacted with this region, and Sp1 knockdown experiments showed that Sp1 critically regulated ZAG expression. Furthermore, ZAG increased the active form of RhoA, which was determined by pull-down assay. Increased serum ZAG concentrations induced, at least partly, by Sp1 may cause an increase in vascular tone through the activation of RhoA and contribute to elevated blood pressure.
锌-α2-糖蛋白（ZAG）（分子量 = 41 kDa）是人类血浆α2组分中的一种成分，据报道与多种疾病相关，如癌症和代谢综合征。ZAG也被认为是脂质代谢的重要调节因子。然而，关于血清ZAG水平与代谢综合征指标之间的相关性知之甚少。通过酶联免疫吸附测定分析的326名年龄在17至79岁之间（236名男性和90名女性）进行年度健康检查的受试者血清ZAG浓度与收缩压和舒张压呈正相关。通过荧光素酶报告基因和电泳迁移率变动分析，发现调节ZAG基因表达的核心启动子区域存在于-110至-101之间。转录因子Sp1与该区域相互作用，Sp1敲低实验表明Sp1对ZAG表达起关键调节作用。此外，通过下拉测定确定ZAG增加了RhoA的活性形式。至少部分由Sp1诱导的血清ZAG浓度升高可能通过激活RhoA导致血管张力增加，并导致血压升高。
