| First Author | Zhou J | Year | 2014 |
| Journal | J Thromb Haemost | Volume | 12 |
| Issue | 11 | Pages | 1890-7 |
| PubMed ID | 25156521 | Mgi Jnum | J:278499 |
| Mgi Id | MGI:6357145 | Doi | 10.1111/jth.12709 |
| Citation | Zhou J, et al. (2014) The disulfide isomerase ERp57 is required for fibrin deposition in vivo. J Thromb Haemost 12(11):1890-7 |
| abstractText | BACKGROUND: ERp57 is required for platelet function; however, whether ERp57 contributes to fibrin generation is unknown. METHODS AND RESULTS: Using an inhibitory anti-ERp57 antibody (mAb1), Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice, and mutants of ERp57, we analyzed the function of ERp57 in laser-induced thrombosis. Fibrin deposition was decreased in Pf4-Cre/ERp57(fl/fl) mice, consistent with a role for platelet ERp57 in fibrin generation. Fibrin deposition was further decreased with infusion of mAb1 and in Tie2-Cre/ERp57(fl/fl) mice, consistent with endothelial cells also contributing to fibrin deposition. Infusion of eptibifatide inhibited platelet and fibrin deposition, confirming a role for platelets in fibrin deposition. Infusion of recombinant ERp57 corrected the defect in fibrin deposition but not platelet accumulation, suggesting a direct effect of ERp57 on coagulation. mAb1 inhibited thrombin generation in vitro, consistent with a requirement for ERp57 in coagulation. Platelet accumulation was decreased to similar extents in Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice and normal mice infused with mAb1. Infusion of completely inactivated ERp57 or ERp57 with a non-functional second active site inhibited fibrin deposition and platelet accumulation, indicating that the isomerase activity of the second active site is required for these processes. CONCLUSION: ERp57 regulates thrombosis via multiple targets. |
