Role of FcRγ and factor XIIIA in coated platelet formation

Jobe, Shawn M.; Leo, Lorie; Eastvold, Joshua S.; Dickneite, Gerhard; Ratliff, Timothy L.; Lentz, Steven R.; Paola, Jorge Di

doi:10.1182/blood-2005-03-1223

Cited by 45 publications

(70 citation statements)

References 21 publications

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“…34 The TG2-null liver treated with CCl 4 fails to clear the necrotic tissue and exhibits a progressive accumulation of ECM with an elevated number of both activated hepatic stellate cells and inflammatory cells, suggesting a protective role for TG2 in liver injury. 35 Thus, both FXIII and TG2 are apparently involved in adult tissue injury and remodeling, 25 and the precise contribution of each molecule to these processes needs to be defined.…”

Section: Discussionmentioning

confidence: 97%

Critical Role of Factor XIII in the Initial Stages of Carbon Tetrachloride–Induced Adult Liver Remodeling

Tsujimoto

Moriya

Sakai

et al. 2011

The American Journal of Pathology

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The transglutaminase-mediated, covalent cross-linking of proteins is an essential step in tissue remodeling after injury. This process provides tissues with extra rigidity and resistance against proteolytic degradation. Plasma coagulation factor XIII (FXIII) is a transglutaminase that promotes cross-linking of the extracellular matrix (ECM) components fibrin and fibronectin to form a provisional matrix in response to tissue damage. However, the functional requirement for this FXIII-mediated cross-linked provisional matrix in adult tissue remodeling remains to be defined. Although it has been proposed that the formation FXIII-mediated fibrin-fibronectin provisional matrix is a critical step for ECM remodeling, we show in an FXIII subunit A-deficient murine model of acute liver injury that the lack of FXIII subunit A did not interfere with collagen reconstruction and resolution after liver injury. Furthermore, FXIIIA deficiency caused significantly increased hepatocyte apoptosis and a delay in hepatocyte regeneration after injury, which were accompanied by a significantly high induction of p53 expression. These findings suggest novel functions of FXIII that the FXIII-mediated covalently crosslinked matrix could promote survival signals for hepatocytes in adult tissue remodeling. Covalent cross-linking between proteins, including in the provisional matrix, is catalyzed by transglutaminases (TGs). This is an important process for tissue remodeling as it generates extra rigidity and a resistance against proteolytic degradation. 1 Plasma coagulation factor Xlll (FXlll), one of the TG family members, circulates as a heterotetramer composed of two catalytic A subunits (FXIII A) and two noncatalytic B subunits (FXIII B) (A 2 B 2 ), which are activated by thrombinmediated cleavage. FXlll is a Ca 2ϩ -dependent TG and catalyzes the formation of -(␥-glutamyl) lysyl crosslinks between specific protein pairs. The cross-linking of fibrin molecules by FXIII to form ␥-chain dimerization is the final step of blood coagulation. 2-4 FXIII also acts on fibronectin-fibronectin and fibrin-fibronectin cross-linking. 5,6 Thus, the action of FXIII in forming covalent crosslinkages clearly plays a vital role in establishing the mechanical stability of the clot, which is critical for homeostatic functions. 2,4 Growing evidence demonstrates that the source of FXIII is not only from plasma: Megakaryocytes/ platelets and monocytes/macrophages also contain cellular FXIII subunit A in their cytoplasm. 7,8 Acute liver injury mediated by the hepatitis virus or hepatotoxins causes massive hepatocyte apoptosis and/or fatal liver damage, and eventually liver transplantation is required. 9,10 Identification of hepatic survival factors is critical for successful therapeutic intervention in liver failure. After acute injury, the liver undergoes a wound-healing response to restore tissue architecture and maintain homeostasis. 11 It requires both a well-orchestrated proliferation of cells and the reconstruction of the extracellular matrix (ECM). A central...

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Section: Discussionmentioning

confidence: 97%

Critical Role of Factor XIII in the Initial Stages of Carbon Tetrachloride–Induced Adult Liver Remodeling

Tsujimoto

Moriya

Sakai

et al. 2011

The American Journal of Pathology

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“…The serotonin-conjugated proteins bind to serotonin binding sites on fibrinogen and thrombospondin (32). Although Factor XIIIa was considered the prime candidate for the transglutaminase involved in coated platelet formation, factor XIIIA−/− mice were found to form coat platelets as well as controls, suggesting the possibility that platelet-derived tissue transglutaminase was involved (33).…”

Section: Transglutaminases and Platelet Functionmentioning

confidence: 99%

Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

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All transglutaminases share the common enzymatic activity of transamidation, or the cross-linking of glutamine and lysine residues to form N epsilon (gamma-glutamyl) lysyl isopeptide bonds. The plasma proenzyme factor XIII is responsible for stabilizing the fibrin clot against physical and fibrinolytic disruption. Another member of the transglutaminase family, tissue transglutaminase or TG2 is abundantly expressed in cardiomyocytes, vascular cells and macrophages. The transglutaminases have a variety of functions independent of their transamidating activity. For example, TG2 binds and hydrolyzes GTP, thereby fostering signal transduction by several G protein coupled receptors. Accumulating evidence points to novel roles for factor XIII and TG2 in cardiovascular biology including: (a) modulating platelet activity, (b) regulating glucose control, (c) contributing to the development of hypertension, (d) influencing the progression of atherosclerosis, (e) regulating vascular permeability and angiogenesis (f) and contributing to myocardial signaling, contractile activity and ischemia/reperfusion injury. In this review, we summarize the cardiovascular biology of two members of the family of transglutaminases, Factor XIII and TG2.

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“…Mice were killed with 100% CO 2 . Whole blood was obtained by cardiac puncture and washed platelets were isolated as previously described (40,41).…”

Section: Methodsmentioning

confidence: 99%

Platelet biogenesis and functions require correct protein O-glycosylation

Wang¹,

Jobe

Ding³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Platelets express a variety of membrane and secreted glycoproteins, but the importance of glycosylation to platelet functions is poorly understood. To explore the importance of O-glycosylation, we generated mice with a targeted deletion of Cosmc in murine endothelial/hematopoietic cells (EHC) (EHC Cosmc −/ y ). X-linked Cosmc encodes an essential chaperone that regulates protein O-glycosylation. This targeted mutation resulted in lethal perinatal hemorrhage in the majority of mice, and the surviving mice displayed severely prolonged tail-bleeding times and macrothrombocytopenia. EHC Cosmc − /y platelets exhibited a marked decrease in GPIb-IX-V function and agonist-mediated integrin αIIbβ3 activation, associated with loss of interactions with von Willebrand factor and fibrinogen, respectively. Significantly, three O-glycosylated glycoproteins, GPIbα, αIIb, and GPVI normally on platelet surfaces that play essential roles in platelet functions, were partially proteolyzed in EHC Cosmc − /y platelets. These results demonstrate that extended O-glycans are required for normal biogenesis of the platelets as well as the expression and functions of their essential glycoproteins, and that variations in O-glycosylation may contribute to altered hemostasis.

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Role of FcRγ and factor XIIIA in coated platelet formation

Cited by 45 publications

References 21 publications

Critical Role of Factor XIII in the Initial Stages of Carbon Tetrachloride–Induced Adult Liver Remodeling

Critical Role of Factor XIII in the Initial Stages of Carbon Tetrachloride–Induced Adult Liver Remodeling

Roles of transglutaminases in cardiac and vascular diseases

Platelet biogenesis and functions require correct protein O-glycosylation

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