Thymosin β₄is released from human blood platelets and attached by factor XIIIa (transglutaminase) to fibrin and collagen

Abstract

The beta-thymosins constitute a family of highly conserved and extremely water-soluble 5 kDa polypeptides. Thymosin beta4 is the most abundant member; it is expressed in most cell types and is regarded as the main intracellular G-actin sequestering peptide. There is increasing evidence for extracellular functions of thymosin beta4. For example, thymosin beta4 increases the rate of attachment and spreading of endothelial cells on matrix components and stimulates the migration of human umbilical vein endothelial cells. Here we show that thymosin beta4 can be cross-linked to proteins such as fibrin and collagen by tissue transglutaminase. Thymosin beta4 is not cross-linked to many other proteins and its cross-linking to fibrin is competed by another family member, thymosin beta10. After activation of human platelets with thrombin, thymosin beta4 is released and cross-linked to fibrin in a time- and calcium-dependent manner. We suggest that thymosin beta4 cross-linking is mediated by factor XIIIa, a transglutaminase that is coreleased from stimulated platelets. This provides a mechanism to increase the local concentration of thymosin beta4 near sites of clots and tissue damage, where it may contribute to wound healing, angiogenesis and inflammatory responses.

Evaluating the relevance of the platelet transcriptome

“…4 These 3 messages were thymosin ␤ 4 , neurogranin, and ␤-globin. 1 Thymosin ␤ 4 and neurogranin protein are also found in platelets, 1,5 however, which is consistent with observations that platelets express gene products that are also present in other cell lineages. 2,3,6,7 Moreover, Gnatenko et al 1 took rigorous measures to account for contributions by leukocytes and red blood cells, and provided persuasive evidence that the thymosin ␤ 4 and neurogranin transcripts are derived from platelets.…”

Roles of transglutaminases in cardiac and vascular diseases

“…Factor XIIIa also cross-links the two receptors (157). Platelets that are activated by thrombin release thymosin beta 4 which is cross-linked by factor XIIIa to collagen and fibrin (158). Thymosin beta 4 has roles in promoting angiogenesis by supporting endothelial cell attachment, spreading and migration (158).…”

“…Platelets that are activated by thrombin release thymosin beta 4 which is cross-linked by factor XIIIa to collagen and fibrin (158). Thymosin beta 4 has roles in promoting angiogenesis by supporting endothelial cell attachment, spreading and migration (158). Furthermore, FXIIIa downregulates thrombospondin-1, an inhibitor of angiogenesis (159).…”

Increased Plasma Concentrations of Cytoskeletal and Ca2+-Binding Proteins and Their Peptides in Psoriasis Patients

“…In addition, tissue and plasma transglutaminases were recently suggested to be able to incorporate Thb4 into fibrinogen and fibrin molecules (38,39 ). Huff et al suggested that such binding provides a mechanism for increasing the local Thb4 concentration near sites of clotting and tissue damage (39 ).…”