Transforming growth factor-beta-induced protein (TGFBIp/beta ig-h3) activates platelets and promotes thrombogenesis.
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.
Kim
Ha-Jeong
HJ
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Kim
Pan-Kyung
PK
Bae
Sang Mun
SM
Son
Hye-Nam
HN
Thoudam
Debraj Singh
DS
Kim
Jung-Eun
JE
Lee
Byung-Heon
BH
Park
Rang-Woon
RW
Kim
In-San
IS
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
D003094:Collagen; D004837:Epinephrine; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein