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

S. A. Maroney, J. P. Ferrel, S. Pan, T. A. White, R. D. Simari, J. H. Mcvey, Alan E. Mast

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Background: 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. Methods and Results: Sequence homology demonstrates that TFPIα existed over 430Ma 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1106-1115
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume7
Issue number7
DOIs
StatePublished - 2009

Keywords

  • Alternative splicing
  • TFPI
  • Tissue factor pathway inhibitor

ASJC Scopus subject areas

  • Hematology

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    Maroney, S. A., Ferrel, J. P., Pan, S., White, T. A., Simari, R. D., Mcvey, J. H., & Mast, A. E. (2009). Temporal expression of alternatively spliced forms of tissue factor pathway inhibitor in mice. Journal of Thrombosis and Haemostasis, 7(7), 1106-1115. https://doi.org/10.1111/j.1538-7836.2009.03454.x