Platelets, 2025 Dec;36(1):2455743. doi: 10.1080/09537104.2025.2455743.
题目：
Extracellular thiol isomerase ERp5 regulates integrin αIIbβ3 activation by inhibition of fibrinogen binding
作者：
Kaifei Sun# 1, Yaqiong Zhang# 1, Aizhen Yang# 1, Yuxin Zhang 1 2, Zhenzhen Zhao 1, Xiaofeng Yan 1, Yi Lu 3, Yue Han 4, Depei Wu 4, Freda Passam 5, Jingyu Zhang 2, Yi Wu 1
单位：
1 Cyrus Tang Medical Institute, The Fourth Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
2 Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
3 Hunan Sinozex Biosciences Co. Ltd, Changsha, China.
4 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Suzhou, China.
5 Department of Haematology, Royal Prince Alfred Hospital, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
#Contributed equally.
摘要：
Recent studies have shown that anti-ERp5 antibodies inhibit platelet activation and thrombus formation; Moreover, ERp5-deficient platelets exhibit enhanced platelet reactivity via regulation of endoplasmic reticulum (ER) stress. In this study, we used a new ERp5-knockout mouse model as well as recombinant ERp5 (rERp5) protein, to examine the role of ERp5 in platelet function and thrombosis. Although platelet-specific ERp5-deficient mice had decreased platelet count, the mice had shortened tail-bleeding times and enhanced platelet accumulation in FeCl3-induced mesenteric artery injury, compared with wild-type mice. Using platelet-specific ERp5-deficient mice, we found that ERp5 deficiency increased platelet aggregation, granule secretion, and integrin αIIbβ3 activation. Wild-type recombinant ERp5 protein (rERp5-wt) and inactive mutant ERp5 protein (rERp5-mut) both inhibited human platelet aggregation and the binding of fibrinogen to human platelets, indicating that ERp5 protein interferes with the interaction between integrin αIIbβ3 and its ligand fibrinogen, and its enzymatic activity is not required for this process. Consistently, wild-type mice injected with rERp5-wt or rERp5-mut protein had prolonged tail-bleeding times. Our results provide important evidence that platelet ERp5 negatively regulates platelet activation and thrombus formation, via steric hindrance interfering with integrin αIIbβ3 ligation.