Temporal expression of alternatively spliced forms of tissue factor pathway inhibitor in mice.

Temporal expression of alternatively spliced forms of tissue factor pathway inhibitor in mice.
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DOI:
10.1111/j.1538-7836.2009.03454.x
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发表时间:
2009-07
期刊:
Journal of thrombosis and haemostasis : JTH
影响因子:
--
通讯作者:
Mast AE
Mast AE
中科院分区:
其他
文献类型:
--
作者:
Maroney SA;Ferrel JP;Pan S;White TA;Simari RD;McVey JH;Mast AE

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小鼠组织因子途径抑制剂 (TFPI) 以三种选择性剪接同工型产生,其结构域结构和细胞表面结合机制不同。小鼠中 TFPI 同工型的组织表达被表征为鉴定其生理功能的第一步。序列同源性表明 TFPIα 存在超过 430 Ma,而 TFPIβ 和 TFPIγ 的进化时间更晚。心脏和肺的原位杂交研究没有发现任何细胞专门表达单一亚型。尽管我们之前的研究表明,TFPIα mRNA 在小鼠组织中比 TFPIβ 或 TFPIγ mRNA 更普遍,但蛋白质印迹研究表明 TFPIβ 是成人组织中产生的主要蛋白亚型,而 TFPIα 在胚胎发育和胎盘中表达。与 TFPIβ 作为成人血管床内产生的主要同工型一致,小鼠血浆中的 TFPI 同工型像 SDS-PAGE 中的 TFPIβ 一样迁移,并且小鼠的肝素可释放血浆 TFPIα 池比人类小得多。数据表明,TFPI 的选择性剪接亚型在小鼠组织中以蛋白质生产水平暂时表达。 TFPIα 和 TFPIβ 在胚胎组织和胎盘中产生,而成人组织几乎只产生 TFPIβ。
Mouse tissue factor pathway inhibitor (TFPI) is produced in three alternatively spliced isoforms that differ in domain structure and mechanism for cell surface binding. Tissue expression of TFPI isoforms in mice was characterized as an initial step for identification of their physiological functions. Sequence homology demonstrates that TFPIα existed over 430 Ma while TFPIβ and TFPIγ evolved more recently. In situ hybridization studies of heart and lung did not reveal any cells exclusively expressing a single isoform. Although our previous studies have demonstrated that TFPIα mRNA is more prevalent than TFPIβ or TFPIγ mRNA in mouse tissues, western blot studies demonstrated that TFPIβ is the primary protein isoform produced in adult tissues, while TFPIα is expressed during embryonic development and in placenta. Consistent with TFPIβ as the primary isoform produced within adult vascular beds, the TFPI isoform in mouse plasma migrates like TFPIβ in SDS-PAGE and mice have a much smaller heparin-releasable pool of plasma TFPIα than humans. The data demonstrate that alternatively spliced isoforms of TFPI are temporally expressed in mouse tissues at the level of protein production. TFPIα and TFPIβ are produced in embryonic tissues and in placenta while adult tissues produce almost exclusively TFPIβ.
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