The serum protein α2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
The serum protein α2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
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DOI：
10.1172/jci17202
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发表时间：
2003-08-01
影响因子：
15.9
通讯作者：
Jahnen-Dechent, W
中科院分区：
文献类型：
--
作者：
Schäfer, C;Heiss, A;Jahnen-Dechent, W
异位钙化是许多退行性疾病的常见并发症。在这里，我们确定血清蛋白α（2）-Heremans-Schmid糖蛋白（Ahsg，也称为胎球蛋白-A）作为一个重要的抑制剂异位钙化作用于系统水平。Ahsg缺陷小鼠表型正常，但在富含矿物质和维生素D的饮食和正常饮食中，当缺乏与DBA/2遗传背景相结合时，各种器官发生严重钙化。这种表型与钙和磷酸盐稳态的明显变化无关，但与Ahsg缺陷细胞外液对矿物质形成的抑制活性降低有关。相同的基本原理可能导致许多钙化性疾病，包括钙化耐受，慢性肾衰竭患者的严重全身钙化综合征。总之，我们的数据表明Ahsg作为不需要的矿化抑制剂的关键作用，并提供了一种新的治疗概念，以防止伴随各种疾病的异位钙化。
Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha(2)-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.