Interacts human plasminogen plasminogen activator inhibitor 1. Medical search. Frequent questions

Such treatment was associated with upregulation of invasion- and inflammation-promoting soluble factors, such as matrix metalloproteinase 2 (MMP2), its activator MMP14, tissue inhibitors of matrix metalloproteinase 2 (TIMP2), chemokine ligand 2 (CCL2), and urokinase-type plasminogen activator (uPA), the latter two being linked to the recruitment of the monocytic cells. (biomedcentral.com)
These mice are generated by transplanting human hepatocytes into albumin enhancer-driven urokinase-type plasminogen activator transgenic/severe combined immunodeficiency (uPA/SCID) mice, leading to replacement of the host hepatocytes. (wur.nl)

As an enzyme , it catalyzes the conversion of plasminogen to plasmin , the major enzyme responsible for clot breakdown. (wikidoc.org)
We suggest the potential roles certain integrins, the urokinase plasminogen activator (uPA), its receptor (uPAR), and plasmin may play in the pathogenesis of Alport kidney disease. (hindawi.com)
Heparin sulfate and the less sulfated glycosaminoglycan heparan sulfate enhance human plasminogen (Pg) conversion to plasmin by tissue-type plasminogen activator (t-PA). (duke.edu)
The plasminogen system is composed of the zymogen, plasminogen, the active serine protease, plasmin, and the activators, inhibitors and modulators of plasmin activity. (grantome.com)
These additional substrates of plasmin suggest that the plasminogen system may facilitate cell migration. (grantome.com)
The capacity of plasminogen to influence cell migration depends upon its interaction with plasminogen receptors, a heterogeneous set of cellular proteins with C-terminal lysines that interact with the lysine binding sites (LBS) in the kringle domains of plasmin(ogen). (grantome.com)

Scholars@Duke publication: Kinetic analysis of the effects of heparin and lipoproteins on tissue plasminogen activator mediated plasminogen activation. (duke.edu)
Both heparin and heparan stimulate the activity of t-PA by interacting with the finger domain of t-PA, with association constants of 1 microM and 200 nM, respectively. (duke.edu)
They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins. (lookformedical.com)

This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. (avivasysbio.com)
A member of the serpin superfamily found in plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. (lookformedical.com)

A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. (lookformedical.com)

The flow-dependent adhesion of platelets to those and other extracellular matrix components is stabilized by a panel of integrins, including integrin α 2 β 1 , α IIb β 3 , and α 6 β 1 (adhesive platelet population), while the initial activation of platelets is achieved by signaling via the collagen/laminin receptor, glycoprotein VI (GPVI). (frontiersin.org)
Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. (hindawi.com)
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to be helpful to reduce kidney function decline, particularly when proteinuria exists [ 2 ]. (hindawi.com)
This hypothesis will be tested not only in vitro, but also by examining changes in plasminogen binding and plasminogen receptor expression in vivo. (grantome.com)
The overexpression of miRNA‑375 significantly suppressed the levels of protein expression of ubiquitin‑protein ligase E3A (UBE3A) and Insulin‑like growth factor‑1 receptor (IGF‑1R) in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
Peroxisomal proliferator activator receptor alpha (PPARα) is a ligand-activated transcription factor that plays a major role in the regulation of lipid metabolism. (wur.nl)

Alpha-1-acid glycoprotein 1 is a protein that in humans is encoded by the ORM1 gene. (wikipedia.org)
1989). "Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. (wikipedia.org)
1973). "Structure of 1 -acid glycoprotein. (wikipedia.org)
1993). "Alpha 1-acid glycoprotein expression in human leukocytes: possible correlation between alpha 1-acid glycoprotein and inflammatory cytokines in rheumatoid arthritis" (PDF). (wikipedia.org)
The process of thrombus formation is considered to be initiated by von Willebrand factor (VWF) binding to exposed collagen or laminin in the damaged vessel wall, followed by shear-dependent platelet binding to VWF through the glycoprotein (GP)Ib-V-IX complex ( 1 , 3 , 4 ). (frontiersin.org)
Glycoprotein found in alpha(1)-globulin region in human serum. (lookformedical.com)

Heme/iron-binding proteins, protease inhibitors, proteases, lipocalins and immune-related proteins were the categories most abundantly expressed in females, while glycolytic enzymes, protease inhibitors and lipocalins were the most abundantly expressed in males. (biomedcentral.com)
Extracellular protease inhibitors that are secreted from FIBROBLASTS. (lookformedical.com)

tPA produced by such means are referred to as recombinant tissue plasminogen activator ( rtPA ). (wikidoc.org)

We have studied the transgenic mouse strain, Tyrp-1-TAg, to try to gain insight into possible molecular mechanisms common to pigmented ocular neoplasms occurring spontaneously in the eyes of these mice and human choroidal melanoma. (molvis.org)
Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. (molvis.org)

Insulin-like growth factor-1 (IGF-1), synthesized and secreted by human hepatocytes, is the primary regulator of insulin and serves an important function in regulating the growth and development of the body ( 8 ). (spandidos-publications.com)

The aim of the present study was to determine whether BAY11‑7082, an inhibitor of the NF‑κB pathway, inhibits the expressions of tissue factor (TF) and plasminogen activator inhibitor‑1 (PAI‑1) in AECⅡ in response to TNF‑α. (spandidos-publications.com)
Pulmonary inflammation can damage pulmonary vascular endothelial cells and type-II alveolar epithelial cells (AECII), which further increases the expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) in these cells, thus activating the exogenous coagulation system. (spandidos-publications.com)
In contrast to monocytes, human macrophages did not show increased tissue factor expression upon stimulation with lipopolysaccharide and interferon-γ. (haematologica.org)

Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known. (lookformedical.com)

Alignment of the amino acid sequence of aprotinin with the Kunitz domains of human proteins allowed the identification and design of a family of peptides, named Angiopeps. (aspetjournals.org)
This is the first study describing the production and distribution of ETS-1 and ETS-2 mRNAs and proteins using in situ hybridization and immunohistochemistry in murine ocular tissue sections of normal control eyes and tumoral eyes from mice of the same age. (molvis.org)
The observed crystal packing of the domains provides a plausible model for the association of multiple tandemly linked EGF-like domains in proteins such as fibrillin-1, Notch, and protein S. This model is consistent with the known functional data and suggests a general biological role for these domains. (embl.de)
We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. (oncotarget.com)
This hypothesis postulates that a variety of cellular responses, ranging from cell adhesion to apoptosis to oncogenic transformation, modulates the cell surface to expose proteins with C-terminal lysines that serve as plasminogen receptors. (grantome.com)
Samples are mixed with a cocktail of biotinylated detection antibodies (Step 1) and then incubated with the array membrane which is spotted in duplicate with capture antibodies to specific target proteins (Step 2) . (rndsystems.com)
In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
[ 9 ] All of these proteins interact with complement proteins, particularly C3b and C4b, dissociate the convertase complexes of the classic and alternative pathways, and halt the amplification of the activation process. (medscape.com)

According to a common concept of thrombosis and hemostasis, damage or injury of a vessel wall and ensuing exposure of extracellular matrix components to the blood stream triggers platelets from the circulation to become adherent and to assemble into a thrombus, thus limiting the extravasation of blood ( 1 , 2 ). (frontiersin.org)

The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. (avivasysbio.com)
Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2α (HIF-2α) and 30 kDa HIV Tat-Interacting Protein (TIP30). (cancerindex.org)
Overexpression of IGF-1 in serum and tissue alters the growth of normal cells and causes uncontrolled proliferation, inhibits differentiation and reduces apoptosis, resulting in the incidence and development of malignant tumors ( 10 ). (spandidos-publications.com)

and membrane inhibitor of reactive lysis (MIRL), or CD59. (medscape.com)

Our previous studies indicated that knockdown of the p65 gene or IKKβ inhibited lipopolysaccharide (LPS)-induced upregulation of TF and PAI-1 in rat AECII ( 15 , 16 ), indicating that the NF-κB signaling pathway participates in coagulation and fibrinolysis regulation in LPS-treated AECⅡ cells. (spandidos-publications.com)
Dr. Vaughan, Zoe's CSO, has worked with this community since 2015 when he discovered community members with a rare, loss-of-function mutation for the gene that codes for PAI-1, the main inhibitor of the fibrinolytic system. (vitadao.com)
Two transcript variants encoding distinct isoforms have been identified for the ZO-1 gene. (thermofisher.com)
Our results support the major role of PPARα in regulating hepatic lipid metabolism, highlight the more modest effect of PPARα activation on gene regulation in human liver compared to mouse liver, and indicate that PPARα may have a suppressive effect on DNA synthesis in human liver. (wur.nl)

However, one pitfall observed throughout the years in in vitro and in in a multitude of human trials in vivo , is the resistance of cancer cell lines to hTRAIL-induced apoptosis. (csuohio.edu)
It has a high affinity KD (0.2 nM) and converts active PAI-1 to substrate PAI-1, which has been confirmed in vitro and in vivo. (vitadao.com)
In Aim 2, the presumed contribution of the LBS within the plasminogen kringles to the fibrinolytic and cell migratory functions of plasminogen will be tested in vivo. (grantome.com)
These studies will utilize plasminogen derivatives lacking specific kringles, either prepared by biochemical approaches or expressed as transgenes in P1g-/- mice to determine how the LBS contribute to the biological functions of plasminogen in vivo. (grantome.com)
In Aim 3, the influence of these two biological modifiers on the functions of plasminogen will be analyzed in vivo using mice expressing apo(a) or deficient in TAR. (grantome.com)
The research contained in this thesis first sought to improve our current knowledge on the transcriptional regulation by peroxisome proliferator-activated receptors (PPAR)-α activation on human liver in vivo using a novel humanized-liver mouse model. (wur.nl)
However, less is known about the effect of PPARα activation in human liver in vivo. (wur.nl)
A novel model to study in vivo PPARα activation in human liver is a chimeric mouse carrying human liver cells. (wur.nl)

To understand if polarization of macrophages can lead to a procoagulant macrophage subset we polarized human monocyte derived macrophages to a proinflammatory and an alternative activation state. (haematologica.org)

Figure 1: Ligands, receptors and SMADs. (nature.com)

Peritoneal injury initiates a proinflammatory response with the release of cytokines such as tumor necrosis factor-α interleukin-1 interleukin-6 and transforming growth factor-β1 (TGF-β1).8-12 studies using human mesothelial cells 12 have shown that these proinflammatory cytokines individually and synergistically stimulate the production of plasminogen activator inhibitor-1 (PAI-1) and reduce the synthesis of tissue plasminogen activator (tPA). (researchtoactionforum.org)

Hypercoagulability and fibrinolytic inhibition, either systemic or in lung tissue, are important characteristics of acute respiratory distress syndrome (ARDS) ( 1-4 ). (spandidos-publications.com)

Membrane enriched extracts (40 µg lysate) of Caco-2 (Lane 1), Caco-2 treated with IFN Gamma (50 ng/mL for 24hrs) (Lane 2), A-431 (Lane 3), HEL 92.1.7 (Lane 4) and Jurkat (Lane 5). (thermofisher.com)
ZO-1 is a protein located on a cytoplasmic membrane surface of intercellular tight junctions. (thermofisher.com)
In Aim 1, a unifying membrane remodeling hypothesis to explain the regulation of plasminogen binding to cells will be tested. (grantome.com)
The Proteome Profiler Human Angiogenesis Array Kit is a membrane-based sandwich immunoassay. (rndsystems.com)

This TF induction was dependent on signal transducer and activator of transcription-6 signaling and poly ADP ribose polymerase activity. (haematologica.org)

This provokes the release of thromboxane A 2 and the secretion of granular contents including ADP and, via these autocrine agents, the subsequent recruitment of additional flowing platelets, which assemble into a growing thrombus via α IIb β 3 -fibrinogen interactions (aggregating platelet population) ( 1 ). (frontiersin.org)
Since human induced pluripotent stem cell (iPSC)-platelet products can be supplied independently from the donor, it is expected to complement current platelet products. (biomedcentral.com)
Based on these developments, we initiated the first-in-human clinical trial of iPSC-derived platelets to a patient with alloimmune platelet transfusion refractoriness (allo-PTR) using an autologous product. (biomedcentral.com)
Moreover, alloantibodies against human leukocyte antigen class I (HLA-I) and to a lesser extent to human platelet antigen (HPA) cause alloimmune platelet transfusion refractoriness (allo-PTR) in 5-15% of patients receiving platelet transfusion. (biomedcentral.com)

Our lead antibody was raised against human PAI-1 and is reactive towards human, mouse, and rat PAI-1. (vitadao.com)

apelin/APJ and PAI-1 synergistically antagonize each other. (vitadao.com)

The first program is PAI-1 biologic inhibitors with high target selectivity and affinity, relevant for diseases including elevated FGF23 syndromes and metabolic disorders. (vitadao.com)
Diseases associated with ZO-1 dysfunction include Celiac Disease and Congenital Nephrotic Syndrome. (thermofisher.com)

The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)

Tissue plasminogen activator (abbreviated tPA or PLAT ) is a protein involved in the breakdown of blood clots . (wikidoc.org)

BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. (oncotarget.com)

Classical polarization is usually associated with a proinflammatory response, including the increased production of tumor necrosis factor (TNF)-α, IL-1, and IL-6. (haematologica.org)
Choroidal melanoma is the most common primary malignant ocular tumor in human adults. (molvis.org)
Elimination of the primary tumor, either by irradiation or by surgery, shifts the balance towards pro-angiogenesis and growth of the lung metastases (Table 1 ) (Camphausen et al. (biomedcentral.com)
A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human breast tumor cell line. (embl.de)

ZO-2 and ZO-3 are ubiquitously expressed within epithelial tight junctions, and unlike ZO-1, which is also expressed at cell junctions of cardiac myocytes, ZO-2 is not expressed in nonepithelial tissue. (thermofisher.com)

3. Kalafatis, M., Takahashi, Y., Girma, J.P., and Meyer, D. Localization of a collagen interactive domain of human von Willebrand Factor between amino acid residues Gly 911 and Glu 1365. (csuohio.edu)

With this seed round, Zoe plans to accomplish the following: lead selection, lead optimization, and preclinical results to support indication selection and a series A. Zoe has an exclusive option on a panel of PAI-1 murine monoclonal antibodies and antibodies developed by Dr. Paul Declerck at KU Leuven in Belgium (Zoe's scientific advisor & a long-time collaborator of Dr. Vaughan's). (vitadao.com)

ETS-1 and ETS-2 mRNA and protein levels were much higher in the ocular tissues of Tyrp-1-TAg mice than in control ocular tissues from wild-type mice. (molvis.org)
We also demonstrated upregulation of ETS-1 and ETS-2 target expressions in Tyrp-1-TAg mice when comparing with the same target expressions in control mice. (molvis.org)
Unlike cancer arising in the human population, tumors in genetically engineered mouse models arise in mice with well defined genetic backgrounds where genetic variability can be minimized. (molvis.org)
The development of Pig1 mice has provided a direct means to assess the functions of plasminogen in cell migration, and support is evolving for this role. (grantome.com)
Model systems to study PPARα in human liver vary from hepatoma cell lines, human primary hepatocytes, human precision cut liver slices, and mice expressing human PPARα. (wur.nl)

1 Some tissue macrophages and precursors are already established embryonically in the yolk sac and fetal liver before the onset of definitive hematopoiesis. (haematologica.org)
Mechanistically, HILPDA acts an inhibitor of ATGL-mediated lipolysis in macrophages. (wur.nl)
Treatment with the ATGL inhibitor Atglistatin rescued lipid accumulation inside lipid droplets in HILPDA-deficient macrophages. (wur.nl)

However,molecules that interact with this protein have not yet been identified. (researchtoactionforum.org)
Biological modifiers of LBS activity, molecules that interfere with their function, could exert profound effects on the plasminogen system. (grantome.com)

21(1): 802, 2023 11 10. (bvsalud.org)

Taken together, these studies seek to bring insights into the physiological and pathophysiological roles of the plasminogen system and its regulation. (grantome.com)

The expression of TF and PAI‑1 were determined using western blotting and reverse transcription‑quantitative PCR. (spandidos-publications.com)
The role of two members of the ETS (E26 avian leukemia oncogene) family of transcription factors, ETS-1 and ETS-2, has been investigated in many cancers but has not yet been studied in ocular tumors. (molvis.org)

This interaction was modeled on a demonstrated interaction between Thrombin from an unspecified species and human PAR1. (uth.edu)

Human tPA has a molecular weight of ~70 kDa in the single-chain form. (wikidoc.org)

Marked up- and down-regulation of plasminogen binding to cells have been demonstrated, but the mechanisms underlying these changes remain obscure. (grantome.com)
Regulation of angiogenesis in repair 2.4.1. (docksci.com)

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. (oncotarget.com)

According to the current top level development plan the IND for the PAI-1 antibody is planned for late early 2025, for the APJ agonist the IND is scheduled for late 2024 - early 2025 (see figures below). (vitadao.com)
The following product was used in this experiment: ZO-1 Monoclonal Antibody (ZO1-1A12) from Thermo Fisher Scientific, catalog # 33-9100, RRID AB_2533147. (thermofisher.com)
Western blot was performed using Anti-ZO-1 Monoclonal Antibody (ZO1-1A12) (Product # 33-9100) and a 225 kDa band corresponding to ZO-1 was observed across along with uncharacterized band. (thermofisher.com)

Decades of research have demonstrated that serum concentrations of blood lipids are associated with increased risk for cardiovascular disease and mortality [ 1 - 4 ]. (cdc.gov)

Identification of heregulin, a specific activator of p185erbB2. (embl.de)
1. OVERVIEW The search for specific agents to improve healing is as old as the practice of medicine. (docksci.com)

In support of this notion, mutations in the components of the TGFβ signaling cascade have been identified in a number of human cancers, including hereditary nonpolyposis colon cancer, hepatocellular carcinoma (HCC), and pancreatic and ovarian cancer [ 10 ] . (encyclopedia.pub)

Anatomy22

Organisms9

Diseases21

Chemicals and Drugs108

Analytical, Diagnostic and Therapeutic Techniques and Equipment32

Phenomena and Processes41

Disciplines and Occupations1

Information Science3

Health Care5

Urokinase-type plasminogen activator2

Plasmin6

Heparin3

Member of the serpin2

Serine proteinase1

Receptor6

Glycoprotein6

Protease inhibitors2

Recombinant1

Transgenic2

Secreted by human hepatocytes1

Tissue factor3

Serpin1

Proteins8

Extracellular1

Inhibits3

Lysis1

Gene4

Vivo8

Macrophage1

Receptors1

Synthesis1

Fibrinolytic1

Membrane4

Poly ADP ribose1

Platelet4

Reactive1

Synergistically1

Diseases2

Cyclin1

PLAT1

Apoptosis1

Tumor4

Cardiac1

Amino1

Murine1

Mice5

Macrophages3

Molecules2

20231

Roles1

Transcription2

Interaction1

Molecular weight1

Regulation2

20221

Antibody3

Serum1

Specific2

Hepatocellular carcinoma1