Effect of FXIII on monocyte and fibroblast function.
Factor XIII is a plasma transglutaminase that participates in the final stage of the coagulation cascade. Thrombin-activated FXIII (FXIIIa) catalyzes the formation of covalent crosslinks between gamma-glutamyl and epsilon-lysyl residues on fibrin molecules to yield the mature clot. In addition to its role in hemostasis, FXIIIa was previously shown by us to stimulate endothelial cells to exhibit pro-angiogenic activity. In this work, we studied the effect of FXIIIa on other cells that participate in angiogenesis and tissue repair, such as monocytes and fibroblasts. FXIIIa significantly enhanced migration and proliferation, and inhibited apoptosis of monocytes and fibroblasts. Similar to our previous observations with endothelial cells, the stimulating effect of FXIIIa on monocytes and fibroblasts was elicited via its binding to alpha (v)beta (3) integrin leading to cJun upregulation and TSP-1 downregulation. Since monocytes and fibroblasts are essential components of the tissue repair process, the results of this study, together with the proangiogenic activity of FXIIIa, further substantiate a significant role of FXIII in tissue repair.
Dardik
Rima
R
Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer.
Krapp
Tanya
T
Rosenthal
Esther
E
Loscalzo
Joseph
J
Inbal
Aida
A
D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005176:Factor XIII / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016755:Proto-Oncogene Proteins c-jun; D019700:Thrombospondin 1; D005176:Factor XIII