Transforming growth factor-β-induced protein (TGFBIp/β ig-h3) activates platelets and promotes thrombogenesis

Ha Jeong Kim, Pan Kyung Kim, Sang Mun Bae, Hye Nam Son, Debraj Singh Thoudam, Jung Eun Kim, Byung Heon Lee, Rang Woon Park, In San Kim

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23 Citations (Scopus)

Abstract

Transforming growth factor-β-induced protein (TGFBIp)/βig-h3 is a 68-kDa extracellular matrix protein that is functionally associated with the adhesion, migration, proliferation, and differentiation of various cells. The presence of TGFBIp in platelets led us to study the role of this protein in the regulation of platelet functions. Upon activation, platelet TGFBIp was released and associated with the platelets. TGFBIp mediates not only the adhesion and spread of platelets but also activates them, resulting in phosphatidylserine exposure, α-granule secretion, and increased integrin affinity. The fasciclin 1 domains of TGFBIp are mainly responsible for the activation of platelets. TGFBIp promotes thrombus formation on type I fibrillar collagen under flow conditions in vitro and induces pulmonary embolism in mice. Moreover, transgenic mice, which have approximately a 1.7-fold greater blood TGFBIp concentration, are significantly more susceptible to collagen- and epinephrine-induced pulmonary embolism than wild-type mice. These results suggest that TGFBIp, a human platelet protein, plays important roles in platelet activation and thrombus formation. Our findings will increase our understanding of the novel mechanism of platelet activation, contributing to a better understanding of thrombotic pathways and the development of new antithrombotic therapies.

Original languageEnglish
Pages (from-to)5206-5215
Number of pages10
JournalBlood
Volume114
Issue number25
DOIs
Publication statusPublished - 2009 Dec 10
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kim, H. J., Kim, P. K., Bae, S. M., Son, H. N., Thoudam, D. S., Kim, J. E., Lee, B. H., Park, R. W., & Kim, I. S. (2009). Transforming growth factor-β-induced protein (TGFBIp/β ig-h3) activates platelets and promotes thrombogenesis. Blood, 114(25), 5206-5215. https://doi.org/10.1182/blood-2009-03-212415