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Subject | Predicate | Object |
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http://purl.uniprot.org/citations/25503990 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/25503990 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectiveAn aneurysm is an inflammatory vascular condition. Phosphatidylinositol 3-kinases δ is highly expressed in leukocytes, and play a key role in innate immunity. However, the link between phosphatidylinositol 3-kinases δ and aneurysm development has not yet been elucidated.Approach and resultsCarotid ligation unexpectedly induced characteristic aneurysm formation beneath the ligation point in p110δ(D910A/D910A) mice (n=25; P<0.001 versus wild-type). Besides, p110δ inactivation exacerbated CaCl2-induced abdominal aortic aneurysms development. A reverse transcription polymerase chain reaction microarray revealed significant extracellular matrix components degradation and matrix metalloproteinases (MMPs) upregulation in the abdominal aorta of p110δ(D910A/D910A) mice. Similarly, the expression of both collagen I and IV was significantly decreased (n=10; P<0.05 versus wild-type) in carotid artery. Western blot assay confirmed that MMP-12 was significantly upregulated in arteries of p110δ(D910A/D910A) mice (n=10; P<0.01 versus wild-type). In vitro, p110δ inactivation marked increase peritoneal macrophages recruitment and synergistically enhance tumor necrosis factor-α-induced recruitment. A specific phosphatidylinositol 3-kinases δ inhibitor (IC87114) or genetic p110δ inactivation upregulated MMP-12 expression and c-Jun phosphorylation (n=6; P<0.05 versus wild-type macrophages). IC87114 also increased activator protein-1 DNA-binding activity (n=6; P<0.001 versus control) and enhanced the effect of tumor necrosis factor-α on activator protein-1-binding activity (n=5; P<0.01 versus tumor necrosis factor-α treatment groups). Knockdown of c-Jun suppressed the effect of the IC87114 and tumor necrosis factor-α on MMP-12 mRNA expression (n=5 in each group; P<0.01 versus scrRNA treatment groups).ConclusionsOur findings demonstrate that p110δ inactivation leads to extracellular matrix degradation in vessels and promotes aneurysm development by inducing macrophages migration and upregulating the activator protein-1/MMP-12 pathway in macrophages."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.org/dc/terms/identifier | "doi:10.1161/atvbaha.114.304365"xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "He X."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Li W."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Gu Q."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Zhang Q."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Wu T."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Zeng C."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Zheng L."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Xing L."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Gui Y."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Tang F."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Qi C."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/author | "Lan T."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/name | "Arterioscler Thromb Vasc Biol"xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/pages | "368-377"xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/title | "Inactivation of PI3Kdelta induces vascular injury and promotes aneurysm development by upregulating the AP-1/MMP-12 pathway in macrophages."xsd:string |
http://purl.uniprot.org/citations/25503990 | http://purl.uniprot.org/core/volume | "35"xsd:string |
http://purl.uniprot.org/citations/25503990 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25503990 |
http://purl.uniprot.org/citations/25503990 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25503990 |
http://purl.uniprot.org/uniprot/#_B0QZL5-mappedCitation-25503990 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25503990 |