Search

Background Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer. Methods The mRNA and protein expression levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired breast cancer tumors by semi-quantitative real time-PCR and western blotting, respectively. Immunohistochemistry was performed to assess PTOV1 protein expression in 169 paraffin-embedded, archived breast cancer samples. Survival analysis and Cox regression analysis were performed to investigate the clinicopathological significance of PTOV1 expression. Results Our data revealed that PTOV1 was frequently overexpressed in breast cancer cell lines compared to normal human breast epithelial cells and in primary breast cancer samples compared to adjacent noncancerous breast tissues, at both the mRNA and protein levels. Moreover, high expression of PTOV1 in breast cancer is strongly associated with clinicopathological characteristics and estrogen receptor expression status (P = 0.003). Breast cancer patients with higher PTOV1 expression had substantially shorter survival times than patients with lower PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that PTOV1 might be an independent prognostic factor for breast cancer patients (P = 0.005). Conclusions Our study showed that PTOV1 is upregulated in breast cancer cell lines and clinical samples, and its expression was positively associated with progression and aggressiveness of breast cancer, suggesting that PTOV1 could serve as an independent prognostic marker. [ABSTRACT FROM AUTHOR]

Neurostimulation procedures like vagus nerve stimulation (VNS) and deep brain stimulation have been used to treat refractory epilepsy and other neurological disorders. While holding promise, they are invasive interventions with serious complications and adverse effects. Moreover, their efficacies are modest with less seizure free. Acupuncture is a simple, safe, and effective traditional healingmodality for a wide range of diseases including pain and epilepsy. Thalamus takes critical role in sensory transmission and is highly involved in epilepsy genesis particularly the absence epilepsy. Considering thalamus serves as a convergent structure for both acupuncture and VNS and the thalamic neuronal activities can be modulated by acupuncture, we propose that acupuncture could be a promising therapy or at least a screening tool to select suitable candidates for those invasive modalities in the management of refractory epilepsy. [ABSTRACT FROM AUTHOR]

Background and objective Targeted therapy in non-small cell lung cancer (NSCLC) had become a research hotspot. Both of gefitinib and erlotinib had already been recommended as first line treatment in epidermal growth factor receptor (EGFR) mutant advanced NSCLC patients. The study aimed to compare the effectiveness and prognosis of advanced NSCLC with gefitinib or erlotinib, as well as the cost-effectiveness ratio of the two drugs. Methods Data of 66 EGFR mutant NSCLC patients who were included in Guangzhou medical insurance were analyzed. The efficacy and adverse reactions were evaluated. All the patients were followed-up regularly and the cost of the treatment was recorded. Results The median progression free survival (PFS) of all patients was 15.0 months. 49 patients received gefintib and 17 patients had erlotinib. The PFS for the two groups of patients was 17.5 month and 13 months, respectively (P=0.459). 31 (62.3%) patients had rash in gefitinib group, 16 (94.1%) in erlotinib group. Cost-effectiveness ratio (CER) in gefitinib group was 3,027 RMB per month, while 6,800 RMB in erlotinib group. The incremental cost-effectiveness ratio (ICEA) of erlotinib was 2.25 times of gefitinib. Conclusion For EGFR mutant advanced NSCLC patients, equal efficacy and survival benefit were observed in patients with gefitinib and erlotinib. The adverse reaction was milder in gefitinib group than that of erlotinib group. And with Guangzhou medical insurance, gefitinib had a superior cost-effectiveness ratio. [ABSTRACT FROM AUTHOR]

The article presents a study which explores the association between the analgesic effect of electroacupuncture stimulation and synamptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica. It is inferred that electroacupuncture stimulation was made at bilateral Zusanli and Yanglingquan. The impact of ovariectomy on the analgesic effect of electroacupuncture stimulation is outlined.

Integrin αIIbβ3 mediated bidirectional signaling plays a critical role in thrombosis and haemostasis. Signaling mediated by the β3 subunit has been extensively studied, but αIIb mediated signaling has not been characterized. Previously, we reported that platelet granule secretion and TxA2 production induced by αIIb mediated outside-in signaling is negatively regulated by the β3 cytoplasmic domain residues R724KEFAKFEEER734. In this study, we identified part of the signaling pathway utilized by αIIb mediated outside-in signaling. Platelets from humans and gene deficient mice, and genetically modified CHO cells as well as a variety of kinase inhibitors were used for this work. We found that aggregation of TxA2 production and granule secretion by β3Δ724 human platelets initiated by αIIb mediated outside-in signaling was inhibited by the Src family kinase inhibitor PP2 and the PI3K inhibitor wortmannin, respectively, but not by the MAPK inhibitor U0126. Also, PP2 and wortmannin, and the palmitoylated β3 peptide R724KEFAKFEEER734, each inhibited the phosphorylation of Akt residue Ser473 and prevented TxA2 production and storage granule secretion. Similarly, Akt phosphorylation in mouse platelets stimulated by the PAR4 agonist peptide AYPGKF was αIIbβ3-dependent, and blocked by PP, wortmannin and the palmitoylated peptide p-RKEFAKFEEER. Akt was also phosphorylated in response to mAb D3 plus Fg treatment of CHO cells in suspension expressing αIIbβ3-D724 or αIIbβ3E724AERKFERKFE734, but not in cells expressing wild type αIIbβ3. In summary, SFK(s) and PI3K/Akt signaling is utilized by αIIb-mediated outside-in signaling to activate platelets even in the absence of all but 8 membrane proximal residues of the β3 cytoplasmic domain. Our results provide new insight into the signaling pathway used by αIIb-mediated outside-in signaling in platelets. [ABSTRACT FROM AUTHOR]

The article discusses a study which found that the cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region in ovariectomized rats with chronic constriction injury (CCI)-induced neuropathic pain on the sciatic nerve. Analysis revealed that electroacupuncture decreases pain reaction after CCI and reduces synaptic cleft width between hippocampal neurons. It increased post-synaptic density and active zone length in hippocampal neurons.

A depth adjustment method for visual fatigue reduction for depth-image-based rendering (DIBR) system is proposed. One important aspect of the method is that no calibration parameters are needed for adjustment. By analyzing 3D image warping, the perceived depth is expressed as a function of three adjustable parameters: virtual view number, scale factor and depth value of zero parallax setting (ZPS) plane. Adjusting these three parameters according to the proposed parameter modification algorithm when performing 3D image warping can effectively change the perceived depth of stereo pairs generated in DIBR system. As the depth adjustment is performed in simple 3D image warping equations, the proposed method is facilitative for hardware implementation. Experimental results show that the proposed depth adjustment method provides an improvement in visual comfort of stereo pairs as well as generating comfortable stereoscopic images with different perceived depths that people desire. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effects of repeated electroacupuncture of Zusanli (ST36) and Yanglingquan (GB34) on rats with chronic constrictive injury. The study showed increased expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter and muscarinic M&sub1; receptor mRNA in the rats. It also revealed an analgesic effect of repeated electroacupuncture.

CD44 is associated with a high risk of metastasis, recurrence, and drug resistance in various cancers. Here we report that platelet endothelial aggregation receptor 1 (PEAR1) is a CD44 chaperone protein that protected CD44 from endocytosis-mediated degradation and enhances cleavage of the CD44 intracellular domain (CD44-ICD). Furthermore, we found that lysyl oxidase--like protein 2 (LOXL2), an endogenous ligand of PEAR1, bound to the PEAR1-EMI domain and facilitated the interaction between PEAR1 and CD44 by inducing PEAR1 Ser891 phosphorylation in a manner that was independent of its enzyme activity. Levels of PEAR1 protein and PEAR1 phosphorylation at Ser891 were increased in patients with triple- negative breast cancer (TNBC), were positively correlated with expression of LOXL2 and CD44, and were negatively correlated with overall survival. The level of PEAR1 Ser891 phosphorylation was identified as the best independent prognostic factor in TNBC patients. The prognostic efficacy of the combination of PEAR1 phosphorylation at Ser891 and CD44 expression was superior to that of PEAR1 phosphorylation at Ser891 alone. Blocking the interaction between LOXL2 and PEAR1 with monoclonal antibodies significantly inhibited TNBC metastasis, representing a promising therapeutic strategy for TNBC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the NR1H3 gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive. METHODS: Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified NR1H3 as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global Nr1h3-knockout and vascular smooth muscle cell--specific Nr1h3-knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl2; 0.5 mol/L; 42 days). RESULTS: Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II-- or CaCl2-treated mice. Global or vascular smooth muscle cell--specific Nr1h3 knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. Uhrf1, an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II-- and CaCl2-induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATACseq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process. CONCLUSIONS: Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA. [ABSTRACT FROM AUTHOR]

Uterine fibroids are benign gynecologic tumors, and women aged between 30 to 50 years are known to have a high incidence of uterine fibroids. A growing number of pharmacotherapies and minimally invasive organ-preserving treatments have been designed and conducted over the past few years. However, there has not been any therapeutic drugs exhibiting an ideal therapeutic effect and low recurrence rate, such that the surgical treatment continues to be primarily employed in the actual clinical treatment. In general, surgical treatment has been performed as the organ- and fertilitypreserving hysteroscopic or laparoscopic resections of the fibroids. Minimally invasive surgical equipment (e.g., hysteroscopy, traditional porous laparoscopy, trans-umbilical laparoscopy, transvaginal laparoscopy, as well as robot-assisted laparoscopy) has been extensively applied to clinical treatment. Compared with traditional laparotomy, minimally invasive surgical equipment is characterized by minimally invasive surgery, high efficiency and safety. As medical technology has been leaping forward, interventional therapy and radiofrequency ablation can also be employed for treating uterine fibroids. In accordance with the research progress worldwide, the current situation, limitations, and advantages of the treatment of uterine fibroids in patients with fertility requirements are reviewed in this study. [ABSTRACT FROM AUTHOR]

Glucagon-secreting pancreatic a-cells play pivotal roles in the development of diabetes. Glucagon promotes insulin secretion from b-cells. However, the long-term effect of glucagon on the function and phenotype of &#914-cells had remained elusive. In this study, we found that long-term glucagon intervention or glucagon intervention with the presence of palmitic acid downregulated &#914-cell-specific markers and inhibited insulin secretion in cultured &#914-cells. These results suggested that glucagon induced &#914-cell dedifferentiation under pathological conditions. Glucagon blockage by a glucagon receptor (GCGR) monoclonal antibody (mAb) attenuated glucagon-induced &#914-cell dedifferentiation. In primary islets, GCGR mAb treatment upregulated &#914-cell-specific markers and increased insulin content, suggesting that blockage of endogenous glucagon-GCGR signaling inhibited &#914-cell dedifferentiation. To investigate the possible mechanism, we found that glucagon decreased FoxO1 expression. FoxO1 inhibitor mimicked the effect of glucagon, whereas FoxO1 overexpression reversed the glucagon-induced &#914-cell dedifferentiation. In db/db mice and &#914-cell lineage-tracing diabetic mice, GCGR mAb lowered glucose level, upregulated plasma insulin level, increased &#914-cell area, and inhibited &#914-cell dedifferentiation. In aged &#914-cell-specific FoxO1 knockout mice (with the blood glucose level elevated as a diabetic model), the glucose-lowering effect of GCGR mAb was attenuated and the plasma insulin level, &#914-cell area, and &#914-cell dedifferentiation were not affected by GCGR mAb. Our results proved that glucagon induced &#914-cell dedifferentiation under pathological conditions, and the effect was partially mediated by FoxO1. Our study reveals a novel cross talk between a- and &#914-cells and is helpful to understand the pathophysiology of diabetes and discover new targets for diabetes treatment. [ABSTRACT FROM AUTHOR]

The Src family kinases (SFKs) have been proposed to play stimulatory and inhibitory roles in platelet activation. The mechanisms for these apparently contradictory roles are unclear. Here we show that SFK, mainly Lyn, is important in stimulating a common signaling pathway leading to secretion of platelet granules. Lyn knock-out or an isoform-nonselective SFK inhibitor, PP2, inhibited platelet secretion of both dense and α granules and the secretion-dependent platelet aggregation induced by thrombin, collagen, and thromboxane A2. The inhibitory effect of Lyn knock-out on platelet aggregation was reversed by supplementing granule content ADP, indicating that the primary role of Lyn is to stimulate granule secretion. Inhibitory effect of PP2 on platelet aggregation induced by thrombin and thromboxane A2 were also reversed by supplementing ADP. Furthermore, PP2 treatment or Lyn knock-out diminished agonist-induced Aktactivation and cyclic GMP production. The inhibitory effect of PP2 or Lyn knock-out on platelet response can be corrected by supplementing cyclic GMP. These data indicate that Lyn stimulates platelet secretion by activating the phosphoinositide 3-kinase-Akt-nitric oxide (NO)-cyclic GMP pathway and also provide an explanation why Lyn can both stimulate and inhibit platelet activation. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common primary brain tumor, but its therapeutic effect is not very ideal up to now. The point of this study was to recognize the potential gene involved in lowergrade glioma (LGG) and to promote the treatment and prognosis for LGG patients. Method: During the investigation, we first studied the differential expression and the survival analysis of GNG5 in patients with glioma, LGG, and GBM, respectively. Then, independent prognostic analysis, the clinical relevance characteristics and the differential expressed genes (DEGs) were also evaluated. In addition, Metascape and GSEA analyses were carried out to achieve potential mechanism. Co-expression and immune infiltration analysis were finally conducted. Results: The results indicated that GNG5 as an independent prognostic indicator was negatively associated with the overall survival of LGG patients. Metascape and GSEA analyses showed that GNG5 may participate in complement and coagulation cascades pathway. The co-expression analysis was concluded that GNG5 was positively correlated with the following factors: C4B, PLAU, C1R, C1QC, C4A, SERPINA1, C1QB, CFI, C3. Conclusions: This study demonstrated that the highly expression of GNG5 in LGG may lead to poor prognosis. Besides, our research also revealed that GNG5 may be a promising immune-related biomarker for LGG patients. [ABSTRACT FROM AUTHOR]

Several CGHC motif-containing disulfide isomerases support thrombosis. We here report that endoplasmic reticulum protein 72 (ERp72), with 3 CGHC redox-active sites (ao, a, and a9), supports thrombosis. We generated a new conditional knockout mouse model and found that Tie2-Cre/ERp72fl/fl mice with bloodandendothelial cells lackingERp72had prolonged tail bleeding times and decreased platelet accumulation in laser-induced cremaster arteriole injury and FeCl3-induced mesenteric arterial injury. Fibrin deposition was decreased in the laser injury model. Both platelet and fibrin accumulation defects were fully rescued by infusion of recombinant ERp72 containing functional a and a9CGHC motifs (ERp72(oo-ss-ss)). Infusion of ERp72 containing inactivated a and a9 CGHC motifs (ERp72(ss-oo-oo)) inhibited platelet accumulation and fibrin deposition in wild-type mice. Infusion of ERp72(oo-ss-ss) into b3-null mice increased fibrin deposition in the absence of platelets. ERp72-null platelets had defective aggregation, JON/A binding, P-selectin expression, and adenosine triphosphate (ATP) secretion. The aggregation and ATP secretion defects were fully rescued by ERp72(oo-ss-ss) but partially rescued by ERp72(ss-oo-ss) and ERp72(ss-ss-oo). Aggregation and ATP secretion of human platelets was potentiated by ERp72(oo-ss-ss) but inhibited by ERp72(ss-oo-ss) and ERp72(ss-ss-oo). These data suggest that both the a and a9 active sites are required for platelet function.ERp72boundpoorly tob3-nullmouseplatelets, and the addition of ERp72(oo-ss-ss) to human platelets generated thiols in aIIbb3, suggesting a direct interaction of ERp72 with aIIbb3. Defective aggregation of ERp72-null platelets was recovered by ERp72, but not other thiol isomerases. In summary, ERp72 plays a critical role in platelet function and coagulation through the a and a9 CGHC motifs. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis (EAE), a common model of multiple sclerosis (MS), is mainly mediated by CD4+ T cells with demyelination and neurodegeneration of central nervous system (CNS). The loss of P2Y12 receptor might be associated with the pathogenesis of MS/EAE, but its potential mechanism is still not clear. In this study, more severe EAE developed in P2Y12-knockout (P2Y12-KO) mice compared to WT mice. Knockout of P2Y12 increased expression of IL-17A in the sera and proportion of Th17 cells in spleen and CNS. However, in vitro studies showed that P2Y12 did not influence cell differentiation and proliferation of CD4+ T cells. In bone marrow-derived dendritic cells (BMDCs), loss of P2Y12 significantly increased the production of IL-23 in contrast to the wild-type (WT) BMDCs. FACS analysis indicated that the culture supernatant from P2Y12-deficient DCs promoted more naïve CD4+ T cells to differentiate into Th17 cells. Our finding demonstrated that genetic deletion of P2Y12 receptor broke the balance of Th subtypes by affecting the cytokine profile of BMDCs and resulted in the aggravated EAE, which suggested that P2Y12 may be a potential target in treating MS. [ABSTRACT FROM AUTHOR]

Thrombin is an effector enzyme for hemostasis and thrombosis; however, endogenous regulators of thrombin remain elusive. Cartilage oligomeric matrix protein (COMP), a matricellular protein also known as thrombospondin-5, is essential for maintaining vascular homeostasis. Here, we asked whether COMP is involved in the process of blood coagulation. COMP deficiency shortened tail-bleeding and clotting time and accelerated ferric-chloride--induced thrombosis in mice. The absence of COMP had no effect on platelet count. In contrast, COMP specifically inhibited thrombin-induced platelet aggregation, activation, and retraction and the thrombin-mediated cleavage of fibrinogen. Furthermore, surface plasmon resonance analysis revealed direct thrombin-COMP binding (KD = 1.38 ± 0.24 μM). In particular, blockage of thrombin exosites with compounds specific for exosite I (hirudin and HD1 aptamer) or exosite II (heparin and HD22 aptamer) impaired the COMP-thrombin interaction, indicating a 2-site binding mechanism. Additionally, epidermal growth factor-like repeats (amino acids 84-261) were identified as a COMP binding site for thrombin. Moreover, COMP was expressed in and secreted by platelets. Using bone marrow transplantation and platelet transfusion to create chimeric mice, platelet-derived but not vessel-wall-derived COMP was demonstrated to inhibit coagulation. Taken together, COMP is an endogenous thrombin inhibitor and negative regulator of hemostasis and thrombosis. [ABSTRACT FROM AUTHOR]

Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophilsprimed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40-/- mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM) mice had thrombocythemia and significantly higher proportions of megakaryocytes in bone marrow. Agonist-induced aggregation and spreading on immobilized fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in platelet-rich plasma containing PIRB-TM platelets was also increased. Characterization of signaling confirmed that PIRB associated with phosphatases Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP) or on spreading. The results further revealed that the phosphorylation levels of the linker for activation of T cells, SH2 domain-containing leukocyte protein of 76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with CRP. The phosphorylation levels of FAK Y397 and integrin β3 Y759 were also enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet α-granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2 possess an antithrombotic function by suppressing collagen receptor glycoprotein VI and integrin αIIbβ3-mediated signaling [ABSTRACT FROM AUTHOR]

The platelet protein disulfide isomerase called ERp57 mediates platelet aggregation, but its role in thrombus formation is unknown. To determine the specific role of platelet-derived ERp57 in hemostasis and thrombosis, we generated a megakaryocyte/platelet-specific knockout. Despite normal platelet counts and platelet glycoprotein expression, mice with ERp57-deficient platelets had prolonged tail-bleeding times and thrombus occlusion times with FeCI3-induced carotid artery injury. Using a mesenteric artery thrombosis model, we found decreased incorporation of ERp57-deficient platelets into a growing thrombus. Platelets lacking ERp57 have defective activation of the αllbβ3 integrin and platelet aggregation. The defect in aggregation was corrected by the addition of exogenous ERp57, implicating surface ERp57 in platelet aggregation. Using mutants of ERp57, we demonstrate the second active site targets a platelet surface substrate to potentiate platelet aggregation. Binding of Alexa 488 -labeled ERp57 to thrombin-activated and Mn2+ -treated platelets lacking αllbβ3 was decreased substantially, suggesting a direct interaction of ERp57 with αIIbβ3. Surface expression of ERp57 protein and activity in human platelets increased with platelet activation, with protein expression occurring in a physiologically relevant time frame. In conclusion, platelet-derived ERp57 directly interacts with αllbβ3 during activation of this receptor and is required for incorporation of platelets into a growing thrombus. [ABSTRACT FROM AUTHOR]