Effect of EPCR knockdown by siRNA in human umbilical vein endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE249130 | GEO | 2024/03/01
REPOSITORIES: GEO
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Project description:Procr, also known as EPCR, is a protein C receptor known to function in the platelet coagulation cascade. We have used RNA-seq to examine RNA differential expression between Procr+ and Procr- myoepithelium in mouse mammary gland. Examine RNA differential expression among subsets of freshly sorted mouse mammary gland myoepithelium.
2014-10-31 | E-GEOD-58088 | biostudies-arrayexpress
Project description:Procr, also known as EPCR, is a protein C receptor known to function in the platelet coagulation cascade. We have used RNA-seq to examine RNA differential expression between Procr+ and Procr- myoepithelium in mouse mammary gland.
2014-10-31 | GSE58088 | GEO
Project description:Cell purification technology combined with whole transcriptome sequencing and small molecule agonist of hematopoietic stem cell self-renewal has allowed us to identify the endothelial protein c receptor protein (EPCR) as a surface maker that defines a rare subpopulation of human cells which is highly enriched for stem cell activity in vivo. EPCR-positive cells exhibit a robust multi-lineage differentiation potential and serial reconstitution in immunocompromised mice. In culture, most if not all of the HSC activity is detected in the EPCR+ subset, arguing for the stability of this marker on the surface of cultured cells, a feature not found with more recently described markers such as CD49f. Functionally EPCR is essential for human HSC activity in vivo. Cells engineered to express low EPCR expression proliferate normally in culture but lack the ability to confer long-term reconstitution. EPCR is thus a stable marker for human HSC. Its exploitation should open new possibilities in our effort to understand the molecular bases behind HSC self-renewal.
2017-06-22 | GSE77128 | GEO
Project description:Background-The endothelial protein C receptor (EPCR) plays an important role within the protein C (PC) pathway in regulating coagulation and inflammation. Recently, we described a novel mechanism of EPCR release from the surface of primary physiological cells. Induced by exogenous activated protein C (APC), EPCR is released in microparticulate form. Its bound APC retains proteolytic anticoagulant activity and we now hypothesise that this microparticulate EPCR-APC complex can also cleave endothelial protease activated receptor 1 (PAR1) to modulate inflammation and cytoprotection. Methods & Results-The gene profiling effect on human endothelial cells by 40nM APC, in free or microparticulate form, was assessed. Transcript profile results showed upregulation of anti-apoptotic and inflammatory genes by APC in either form, which were confirmed by RT-PCR. These translated into increased GM-CSF and interleukin 8 secretion and cytoprotection against staurosporine-induced apoptosis. PC or PAR1 antagonism reversed these results to demonstrate that induced effects by microparticles were APC specific and PAR1-dependent. Further analysis of human plasma from septic patients, by confocal microscopy and ELISA, showed evidence of circulating microparticle-associated EPCR during recombinant APC treatment. Functional coagulation and cellular studies demonstrate that these express APC-specific effects on anticoagulation with PAR1-mediated gene induction and anti-apoptotic function. Conclusions-APC induction of microparticle-associated EPCR release can occur in vivo. These microparticles could potentially disseminate the function of the EPCR-APC complex to PAR1 on different cells and vascular sites. Keywords: pre versus rhAPC-treatment mp in vivo MP were isolated from sepsis patients pre and during-rhAPC treatment. MP were counted by FACS using CD13 positivity and same number of mp was used in pre and during treatment comparisons. HUVEC were incubated with the in vivo mps according to mp number or apc content, and controls for both were done using non-treated patients or free-apc. The role of apc and par1 was analysed by including apc blocking antibody or par1 antaginist peptide respectively.
2010-06-24 | E-GEOD-5661 | biostudies-arrayexpress
Project description:Background-The endothelial protein C receptor (EPCR) plays an important role within the protein C (PC) pathway in regulating coagulation and inflammation. Recently, we described a novel mechanism of EPCR release from the surface of primary physiological cells. Induced by exogenous activated protein C (APC), EPCR is released in microparticulate form. Its bound APC retains proteolytic anticoagulant activity and we now hypothesise that this microparticulate EPCR-APC complex can also cleave endothelial protease activated receptor 1 (PAR1) to modulate inflammation and cytoprotection. Methods & Results-The gene profiling effect on human endothelial cells by 40nM APC, in free or microparticulate form, was assessed. Transcript profile results showed upregulation of anti-apoptotic and inflammatory genes by APC in either form, which were confirmed by RT-PCR. These translated into increased GM-CSF and interleukin 8 secretion and cytoprotection against staurosporine-induced apoptosis. PC or PAR1 antagonism reversed these results to demonstrate that induced effects by microparticles were APC specific and PAR1-dependent. Further analysis of human plasma from septic patients, by confocal microscopy and ELISA, showed evidence of circulating microparticle-associated EPCR during recombinant APC treatment. Functional coagulation and cellular studies demonstrate that these express APC-specific effects on anticoagulation with PAR1-mediated gene induction and anti-apoptotic function. Conclusions-APC induction of microparticle-associated EPCR release can occur in vivo. These microparticles could potentially disseminate the function of the EPCR-APC complex to PAR1 on different cells and vascular sites. Keywords: free apc versus mp-apc MP were isolated from huvec after estimulation with apc; the apc content of the mp was estimated by chromogenic substrate and a standard curve. 40nM apc on mp was used for estimulation of huvec for 4 hours for study of gene expression. APC relevance was studied by blocking experiments with antibody and par1 involvement was studied by including a par1 antagonist. All experiments were done in triplicate. A basline control was obtained by looking at the profile of non-estimulated cells under the same conditions.
2010-06-24 | E-GEOD-5660 | biostudies-arrayexpress
Project description:Background-The endothelial protein C receptor (EPCR) plays an important role within the protein C (PC) pathway in regulating coagulation and inflammation. Recently, we described a novel mechanism of EPCR release from the surface of primary physiological cells. Induced by exogenous activated protein C (APC), EPCR is released in microparticulate form. Its bound APC retains proteolytic anticoagulant activity and we now hypothesise that this microparticulate EPCR-APC complex can also cleave endothelial protease activated receptor 1 (PAR1) to modulate inflammation and cytoprotection. Methods & Results-The gene profiling effect on human endothelial cells by 40nM APC, in free or microparticulate form, was assessed. Transcript profile results showed upregulation of anti-apoptotic and inflammatory genes by APC in either form, which were confirmed by RT-PCR. These translated into increased GM-CSF and interleukin 8 secretion and cytoprotection against staurosporine-induced apoptosis. PC or PAR1 antagonism reversed these results to demonstrate that induced effects by microparticles were APC specific and PAR1-dependent. Further analysis of human plasma from septic patients, by confocal microscopy and ELISA, showed evidence of circulating microparticle-associated EPCR during recombinant APC treatment. Functional coagulation and cellular studies demonstrate that these express APC-specific effects on anticoagulation with PAR1-mediated gene induction and anti-apoptotic function. Conclusions-APC induction of microparticle-associated EPCR release can occur in vivo. These microparticles could potentially disseminate the function of the EPCR-APC complex to PAR1 on different cells and vascular sites. Keywords: pre versus rhAPC-treatment mp in vivo
2010-02-28 | GSE5661 | GEO
Project description:Background-The endothelial protein C receptor (EPCR) plays an important role within the protein C (PC) pathway in regulating coagulation and inflammation. Recently, we described a novel mechanism of EPCR release from the surface of primary physiological cells. Induced by exogenous activated protein C (APC), EPCR is released in microparticulate form. Its bound APC retains proteolytic anticoagulant activity and we now hypothesise that this microparticulate EPCR-APC complex can also cleave endothelial protease activated receptor 1 (PAR1) to modulate inflammation and cytoprotection. Methods & Results-The gene profiling effect on human endothelial cells by 40nM APC, in free or microparticulate form, was assessed. Transcript profile results showed upregulation of anti-apoptotic and inflammatory genes by APC in either form, which were confirmed by RT-PCR. These translated into increased GM-CSF and interleukin 8 secretion and cytoprotection against staurosporine-induced apoptosis. PC or PAR1 antagonism reversed these results to demonstrate that induced effects by microparticles were APC specific and PAR1-dependent. Further analysis of human plasma from septic patients, by confocal microscopy and ELISA, showed evidence of circulating microparticle-associated EPCR during recombinant APC treatment. Functional coagulation and cellular studies demonstrate that these express APC-specific effects on anticoagulation with PAR1-mediated gene induction and anti-apoptotic function. Conclusions-APC induction of microparticle-associated EPCR release can occur in vivo. These microparticles could potentially disseminate the function of the EPCR-APC complex to PAR1 on different cells and vascular sites. Keywords: free apc versus mp-apc
2010-02-28 | GSE5660 | GEO
Project description:We have used RNA-seq to examine RNA differential expression between Procr+ and Procr- vascular endothelial cells in mouse mammary gland
2016-10-31 | GSE69129 | GEO
Project description:T cells bearing gamma delta T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of gamma delta TCRs to such responses is unclear. Here we found that the TCR of a human V gamma4Vdelta5 clone directly bound endothelial protein C receptor (EPCR), which allowed gamma delta T cells to recognize both endothelial cells targeted by cytomegalovirus and epithelial tumors. EPCR is a major histocompatibility complex–like molecule that binds lipids analogously to the antigen-presenting molecule CD1d. However, the V gamma4Vdelta5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by gamma delta T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a gamma delta TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen. 2E9 is an antibody that blocks gd-TCR recognition of human cells that are the targets of the clone LES. 2E9 also stains cells that are targeted by LES. Therefore, to identify the TCR ligand expressed by 2E9-positive cells, Gene Expression was compared in two cell lines that stain with 2E9 (K562 and U937) versus two cell lines that do not (Hutu80 and Huh7).
2012-07-27 | E-GEOD-39709 | biostudies-arrayexpress
Project description:T cells bearing gamma delta T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of gamma delta TCRs to such responses is unclear. Here we found that the TCR of a human V gamma4Vdelta5 clone directly bound endothelial protein C receptor (EPCR), which allowed gamma delta T cells to recognize both endothelial cells targeted by cytomegalovirus and epithelial tumors. EPCR is a major histocompatibility complex–like molecule that binds lipids analogously to the antigen-presenting molecule CD1d. However, the V gamma4Vdelta5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by gamma delta T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a gamma delta TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.
2012-07-28 | GSE39709 | GEO