The role of transglutaminase 2 in stabilizing fibrin clots and supporting hemostasis
Transglutaminases are enzymes with pleiotropic functions in the human body, among them are the A-subunit of coagulation factor XIII (FXIII; FXIII-A) and tissue transglutaminase (TG2). FXIII has a crucial function in clot formation and stabilization. FXIII also contributes to extracellular matrix formation, wound healing and tissue regeneration, a function it shares with TG2. Whether TG2 may also have a role in hemostasis has never been studied in detail. The aim of our project was to study the role of TG2 in clot formation, stabilization and hemostasis. Here, with the use of a microfluidic endothelialized whole blood bleeding model, we detected TG2 and its crosslinking activity at the site of vessel injury, and the addition of exogenous TG2 resulted in its co-localization with the fibrin clot. In turbidimetric clot formation and lysis tests, TG2 delayed clot lysis. Finally, mass-spectrometry and proteomic analyses revealed differences in fibrin chain crosslinking patterns and protein composition of purified and plasma fibrin clots generated in the presence of either FXIII or TG2. Our data suggest that TG2 is present at the site of clot formation upon vessel injury and contributes to fibrin crosslinking and clot stabilization. Hence, TG2 may be able support hemostasis.