Wöltje Michael, Tschöke Beate, von Bülow Verena, Westenfeld Ralf, Denecke Bernd, Gräber Steffen, Jahnen-Dechent Willi
Interdisciplinary Center for Clinical Research (IZKF) BIOMAT, RWTH Aachen University Hospital, Pauwelsstr. 30, D-52074 Aachen, Germany.
J Mol Endocrinol. 2006 Apr;36(2):261-77. doi: 10.1677/jme.1.02001.
Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated and therefore considered a negative acute phase protein. Enhancement of Ahsg expression as a protective serum protein is desirable in several diseases including tissue remodelling after trauma and infection, kidney and heart failure, and cancer. Using reporter gene assays in hepatoma cells combined with electrophoretic mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg. A steroid response unit at position -146/-119 within the mouse Ahsg promoter mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds the hepatocyte nuclear factor 3beta and CCAAT enhancer binding protein beta (C/EBP-beta). The up-regulation is mediated indirectly via glucocorticoid hormone-induced transcriptional up-regulation in C/EBP-beta protein. A high degree of sequence identity in mouse, rat and human Ahsg promoters suggests that the promoter is similarly up-regulated by dexamethasone in all three species. Therefore, our findings suggest that glucocorticoids may be used to enhance the level of Ahsg protein circulating in serum.
α2HS-糖蛋白/胎球蛋白-A（Ahsg）是一种防止软组织钙化的血清蛋白。在创伤和炎症中，Ahsg表达下调，因此被认为是一种负急性期蛋白。在包括创伤和感染后的组织重塑、肾脏和心力衰竭以及癌症在内的多种疾病中，增强Ahsg作为一种保护性血清蛋白的表达是可取的。通过在肝癌细胞中进行报告基因分析并结合电泳迁移率变动分析，我们确定地塞米松可上调肝脏中的Ahsg。小鼠Ahsg启动子中-146/-119位置的类固醇反应元件介导糖皮质激素诱导的Ahsg mRNA增加。它与肝细胞核因子3β和CCAAT增强子结合蛋白β（C/EBP-β）结合。这种上调是通过糖皮质激素诱导的C/EBP-β蛋白转录上调间接介导的。小鼠、大鼠和人类Ahsg启动子中高度的序列同一性表明，在所有这三个物种中，该启动子同样会被地塞米松上调。因此，我们的研究结果表明，糖皮质激素可用于提高血清中循环的Ahsg蛋白水平。
