FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2021850499> ?p ?o ?g. }

• W2021850499 endingPage "16722" @default.
• W2021850499 startingPage "16713" @default.
• W2021850499 abstract "Sickle cell disease (SCD) is characterized by a prothrombotic state. Plasminogen activator inhibitor-1 (PAI-1) is known to modulate fibrinolysis, lung injury/fibrosis, and angiogenesis. However, its role in SCD is less understood, and the molecular mechanisms underlying increased PAI-1 are unknown. Herein, we show a novel link between PAI-1 and sickle erythropoiesis. Plasma PAI-1 levels were high in SCD patients at steady state and in two humanized sickle mouse models, with increased PAI-1 immunolabeling in sickle mouse lung, bronchial epithelial cells, alveolar macrophages, and pulmonary microvascular endothelial cells. Placenta growth factor (PlGF), released at high levels by sickle erythroblasts, induced PAI-1 expression in primary human pulmonary microvascular endothelial cells and monocytes through activation of c-Jun N-terminal kinase (JNK), NADPH oxidase, and hypoxia-inducible factor-1α (HIF-1α). Analysis of the human PAI-1 promoter revealed this induction was mediated by hypoxia-response element (HRE)-1, HRE-2, and distal activator protein (AP-1) sites. We also identify the involvement of c-Jun, c-Jun/c-Fos, and JunD, but not JunB, in binding with AP-1 sites of the PAI-1 promoter upon PlGF induction. Consistent with these findings, levels of PAI-1 were low in PlGF knock-out mice and sickle-PlGF knock-out mice; overexpression of PlGF in normal mice increased circulating PAI-1. In conclusion, we identify a novel mechanism of PAI-1 elevation in SCD. Sickle cell disease (SCD) is characterized by a prothrombotic state. Plasminogen activator inhibitor-1 (PAI-1) is known to modulate fibrinolysis, lung injury/fibrosis, and angiogenesis. However, its role in SCD is less understood, and the molecular mechanisms underlying increased PAI-1 are unknown. Herein, we show a novel link between PAI-1 and sickle erythropoiesis. Plasma PAI-1 levels were high in SCD patients at steady state and in two humanized sickle mouse models, with increased PAI-1 immunolabeling in sickle mouse lung, bronchial epithelial cells, alveolar macrophages, and pulmonary microvascular endothelial cells. Placenta growth factor (PlGF), released at high levels by sickle erythroblasts, induced PAI-1 expression in primary human pulmonary microvascular endothelial cells and monocytes through activation of c-Jun N-terminal kinase (JNK), NADPH oxidase, and hypoxia-inducible factor-1α (HIF-1α). Analysis of the human PAI-1 promoter revealed this induction was mediated by hypoxia-response element (HRE)-1, HRE-2, and distal activator protein (AP-1) sites. We also identify the involvement of c-Jun, c-Jun/c-Fos, and JunD, but not JunB, in binding with AP-1 sites of the PAI-1 promoter upon PlGF induction. Consistent with these findings, levels of PAI-1 were low in PlGF knock-out mice and sickle-PlGF knock-out mice; overexpression of PlGF in normal mice increased circulating PAI-1. In conclusion, we identify a novel mechanism of PAI-1 elevation in SCD." @default.
• W2021850499 created "2016-06-24" @default.
• W2021850499 creator A5014258096 @default.
• W2021850499 creator A5055095007 @default.
• W2021850499 creator A5067822812 @default.
• W2021850499 creator A5069531160 @default.
• W2021850499 creator A5077164584 @default.
• W2021850499 creator A5087991513 @default.
• W2021850499 date "2010-05-01" @default.
• W2021850499 modified "2023-10-18" @default.
• W2021850499 title "Placenta Growth Factor (PlGF), a Novel Inducer of Plasminogen Activator Inhibitor-1 (PAI-1) in Sickle Cell Disease (SCD)" @default.
• W2021850499 cites W147413047 @default.
• W2021850499 cites W1489573122 @default.
• W2021850499 cites W1501125992 @default.
• W2021850499 cites W1875554126 @default.
• W2021850499 cites W1966675928 @default.
• W2021850499 cites W1972422145 @default.
• W2021850499 cites W1972590090 @default.
• W2021850499 cites W1974863193 @default.
• W2021850499 cites W1977320652 @default.
• W2021850499 cites W1977708103 @default.
• W2021850499 cites W1977902516 @default.
• W2021850499 cites W1979959797 @default.
• W2021850499 cites W1980814594 @default.
• W2021850499 cites W1990033742 @default.
• W2021850499 cites W1993243592 @default.
• W2021850499 cites W1994219871 @default.
• W2021850499 cites W2002456771 @default.
• W2021850499 cites W2005712358 @default.
• W2021850499 cites W2006052765 @default.
• W2021850499 cites W2009936217 @default.
• W2021850499 cites W2013336992 @default.
• W2021850499 cites W2016576925 @default.
• W2021850499 cites W2018783141 @default.
• W2021850499 cites W2027837178 @default.
• W2021850499 cites W2032102036 @default.
• W2021850499 cites W2042775328 @default.
• W2021850499 cites W2047797817 @default.
• W2021850499 cites W2051114755 @default.
• W2021850499 cites W2052700106 @default.
• W2021850499 cites W2060937867 @default.
• W2021850499 cites W2063416975 @default.
• W2021850499 cites W2064697340 @default.
• W2021850499 cites W2066023816 @default.
• W2021850499 cites W2080613214 @default.
• W2021850499 cites W2099980063 @default.
• W2021850499 cites W2111983416 @default.
• W2021850499 cites W2114767843 @default.
• W2021850499 cites W2116763746 @default.
• W2021850499 cites W2127265286 @default.
• W2021850499 cites W2139906185 @default.
• W2021850499 cites W2148547093 @default.
• W2021850499 cites W2162158185 @default.
• W2021850499 cites W2170077226 @default.
• W2021850499 cites W2326476344 @default.
• W2021850499 cites W4231307067 @default.
• W2021850499 cites W4237563548 @default.
• W2021850499 cites W4244633958 @default.
• W2021850499 cites W4249758754 @default.
• W2021850499 doi "https://doi.org/10.1074/jbc.m110.101691" @default.
• W2021850499 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2878021" @default.
• W2021850499 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20351105" @default.
• W2021850499 hasPublicationYear "2010" @default.
• W2021850499 type Work @default.
• W2021850499 sameAs 2021850499 @default.
• W2021850499 citedByCount "35" @default.
• W2021850499 countsByYear W20218504992012 @default.
• W2021850499 countsByYear W20218504992013 @default.
• W2021850499 countsByYear W20218504992014 @default.
• W2021850499 countsByYear W20218504992015 @default.
• W2021850499 countsByYear W20218504992016 @default.
• W2021850499 countsByYear W20218504992017 @default.
• W2021850499 countsByYear W20218504992018 @default.
• W2021850499 countsByYear W20218504992019 @default.
• W2021850499 countsByYear W20218504992021 @default.
• W2021850499 countsByYear W20218504992023 @default.
• W2021850499 crossrefType "journal-article" @default.
• W2021850499 hasAuthorship W2021850499A5014258096 @default.
• W2021850499 hasAuthorship W2021850499A5055095007 @default.
• W2021850499 hasAuthorship W2021850499A5067822812 @default.
• W2021850499 hasAuthorship W2021850499A5069531160 @default.
• W2021850499 hasAuthorship W2021850499A5077164584 @default.
• W2021850499 hasAuthorship W2021850499A5087991513 @default.
• W2021850499 hasBestOaLocation W20218504991 @default.
• W2021850499 hasConcept C126322002 @default.
• W2021850499 hasConcept C134018914 @default.
• W2021850499 hasConcept C181199279 @default.
• W2021850499 hasConcept C203014093 @default.
• W2021850499 hasConcept C2776825266 @default.
• W2021850499 hasConcept C2779679481 @default.
• W2021850499 hasConcept C2780675426 @default.
• W2021850499 hasConcept C2781071845 @default.
• W2021850499 hasConcept C502942594 @default.
• W2021850499 hasConcept C55493867 @default.
• W2021850499 hasConcept C71924100 @default.
• W2021850499 hasConcept C86803240 @default.
• W2021850499 hasConceptScore W2021850499C126322002 @default.
• W2021850499 hasConceptScore W2021850499C134018914 @default.

• next