The multi‐functional serpin, protein C inhibitor: beyond thrombosis and hemostasis
The multi‐functional serpin, protein C inhibitor: beyond thrombosis and hemostasis
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DOI：
10.1111/j.1538-7836.2008.03181.x
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发表时间：
2008-12
影响因子：
10.4
通讯作者：
Koji Suzuki
中科院分区：
文献类型：
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作者：
Koji Suzuki
概括。蛋白 C 抑制剂 (PCI) 是丝氨酸蛋白酶抑制剂 (serpin) 家族的成员。 PCI最初被发现是一种活化蛋白C的抑制剂，后来被证明是一种有效的凝血和纤维蛋白溶解抑制剂，例如由尿激酶型纤溶酶原激活剂介导的凝血和纤维蛋白溶解。因此，该蛋白质被称为纤溶酶原激活剂抑制剂-3。它还抑制参与受精的蛋白酶。 PCI 广泛保守，存在于人类、恒河猴、牛、兔、大鼠、小鼠和鸡中。人类 PCI 基因位于染色体 14q32.1 上的一组编码相关丝氨酸蛋白酶抑制剂的基因中。 5'侧翼区的 Sp1 和 AP2 结合位点分别充当其在肝脏中表达的启动子和增强子。 PCI mRNA 在灵长类动物的许多器官中表达，但仅在啮齿类动物的生殖器官中表达。最近使用表达人类基因的转基因小鼠进行的研究表明，PCI 还参与肺重塑、组织再生、血管通透性、肾脏蛋白水解和肿瘤细胞侵袭的调节。还观察到 PCI 具有不依赖于蛋白酶抑制剂的活性，可预防肿瘤细胞的抗血管生成和转移。因此，PCI是一种独特的多功能丝氨酸蛋白酶抑制剂，在多种物种的多个器官和组织的血栓形成和止血中发挥着多种作用。
Summary. Protein C inhibitor (PCI) is a member of the serine protease inhibitor (serpin) family. PCI was initially found to be an inhibitor of activated protein C, and later shown to be a potent inhibitor of blood coagulation and fibrinolysis such as that mediated by urokinase type‐plasminogen activator. Therefore, the protein came to be known as plasminogen activator inhibitor‐3. It also inhibits proteases involved in fertilization. PCI is broadly conserved, and is found in human, rhesus monkey, cow, rabbit, rat, mouse and chicken. The human PCI gene is located on chromosome 14q32.1 in a cluster of genes encoding related serpins. Sp1‐ and AP2‐binding sites in the 5′‐flanking region act as promoter and enhancer, respectively, for its expression in the liver. PCI mRNA is expressed in many organs in primates, but only in the reproductive organs in rodents. Recent studies using transgenic mice expressing the human gene have suggested that PCI is also involved in regulation of lung remodeling, tissue regeneration, vascular permeability, proteolysis in the kidney and tumor cell invasion. A protease inhibitor‐independent activity of PCI, the prevention of anti‐angiogenesis and metastasis of tumor cells, has also been observed. Thus, PCI is a unique multi‐functional serpin playing diverse roles in the thrombosis and hemostasis in multiple organs and tissues of a variety of species.