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小鼠可变剪接组织因子的鉴定与特性分析

Identification and characterization of murine alternatively spliced tissue factor.

作者信息

Bogdanov V Y, Kirk R I, Miller C, Hathcock J J, Vele S, Gazdoiu M, Nemerson Y, Taubman M B

机构信息

Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.

出版信息

J Thromb Haemost. 2006 Jan;4(1):158-67. doi: 10.1111/j.1538-7836.2005.01680.x.

DOI:10.1111/j.1538-7836.2005.01680.x
PMID:16409465
Abstract

Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation and plays a critical role in regulating hemostasis and thrombosis. We have recently reported a naturally occurring, soluble form of human tissue factor (asTF) generated by alternative splicing. This splice variant has a novel C-terminus with no homology to that of the full-length TF (flTF), lacks a transmembrane domain, and is active in the presence of phospholipids. Mouse models offer unique opportunities to examine the relative importance of flTF and asTF in mediating thrombosis, the response to arterial injury, and ischemic damage. To that end, we have identified and characterized murine asTF (masTF). Like the human splice variant, masTF lacks a transmembrane domain and has a unique C-terminus. We have generated antibodies specific to masTF and murine flTF (mflTF) to examine the expression of both forms of TF. masTF antigen is widely and abundantly expressed, with a pattern similar to that of mflTF, in adult tissues, in experimentally induced thrombi, and during development. These studies demonstrate that masTF contributes to the pool of total TF and may thus play an important role in mediating TF-dependent processes.

摘要

组织因子(TF)是一种跨膜糖蛋白,可启动凝血过程,并在调节止血和血栓形成中发挥关键作用。我们最近报道了一种通过可变剪接产生的天然存在的可溶性人组织因子(asTF)。这种剪接变体具有一个与全长TF(flTF)的C末端无同源性的新型C末端,缺乏跨膜结构域,并且在磷脂存在下具有活性。小鼠模型为研究flTF和asTF在介导血栓形成、对动脉损伤的反应以及缺血性损伤中的相对重要性提供了独特的机会。为此,我们已经鉴定并表征了鼠asTF(masTF)。与人类剪接变体一样,masTF缺乏跨膜结构域并具有独特的C末端。我们已经产生了针对masTF和鼠flTF(mflTF)的特异性抗体,以检测两种形式的TF的表达。在成年组织、实验诱导的血栓以及发育过程中,masTF抗原广泛且大量表达,其模式与mflTF相似。这些研究表明,masTF是总TF池的一部分,因此可能在介导TF依赖性过程中发挥重要作用。

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