title: Transforming growth factor-beta-induced protein (TGFBIp/beta ig-h3) activates platelets and promotes thrombogenesis.
abstract: Transforming growth factor-beta-induced protein (TGFBIp)/beta ig-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, alpha-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.
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ha-Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Pan-Kyung
authors.initials: PK
authors.lastname: Kim
authors.forename: Sang Mun
authors.initials: SM
authors.lastname: Bae
authors.forename: Hye-Nam
authors.initials: HN
authors.lastname: Son
authors.forename: Debraj Singh
authors.initials: DS
authors.lastname: Thoudam
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen; D004837:Epinephrine; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015539:Platelet Activation / Q000502:physiology*; D011655:Pulmonary Embolism / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099222:betaIG-H3 Protein
chemical_list: D003094:Collagen; D004837:Epinephrine; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein