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http://purl.uniprot.org/citations/20056911http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20056911http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The angiopoietin (Ang)-Tie-2 system plays a critical role during fetal and adult angiogenesis. Herein, we explored the Tie-2 shedding-related molecular mechanisms and the pathophysiological significance.

Methods and results

By using a mouse hindlimb ischemia model, we observed dissociated expression between the full-length Tie-2 (fTie-2) protein and Tie-2 mRNA in thigh muscles 1 day after an ischemic operation, suggesting that fTie-2 expression was modified through the posttranscriptional regulation in vivo. A soluble form of Tie-2 produced in human umbilical vein endothelial cells was dramatically suppressed by treatment with siRNA-matrix metalloproteinase (MMP) 14 or tissue inhibitor of metalloproteinase 3, resulting in an increase in cellular fTie-2 and thereby enhancing Ang-1-dependent Akt phosphorylation and Akt-dependent endothelial functions, such as Ang-2 downregulation or an increase of endothelial viability. Phorbol-12-myristate-13 acetate (PMA) upregulates MMP-14 mRNA via protein kinase C-extracellular signal-regulated kinase pathways, and enhanced soluble Tie-2 production in an MMP-14-dependent manner, resulting in a reduction of cellular fTie-2. In addition, the PMA-induced soluble Tie-2 was mediated by the protein kinase C-extracellular signal-regulated kinase signaling pathways. Finally, downregulation of tissue inhibitor of metalloproteinase 3 and upregulation of MMP-14 mRNA were confirmed in ischemic thigh muscles 1 day after the operation.

Conclusions

An autocrine linkage between the endothelial protein kinase C-MMP-14 axis and Tie-2 shedding was shown to be a novel regulatory mechanism for the Ang-Tie-2 system and may play a role in modulating endothelial function during angiogenesis."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.109.201111"xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/author"Fujii T."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/author"Suzuki H."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/author"Sueishi K."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/author"Yonemitsu Y."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/author"Onimaru M."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/pages"818-826"xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/title"An autocrine linkage between matrix metalloproteinase-14 and Tie-2 via ectodomain shedding modulates angiopoietin-1-dependent function in endothelial cells."xsd:string
http://purl.uniprot.org/citations/20056911http://purl.uniprot.org/core/volume"30"xsd:string
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