Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/15795331http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15795331http://www.w3.org/2000/01/rdf-schema#comment"

Background

Migration, proliferation, and matrix-degrading protease expression of smooth muscle cells (SMCs) are major features of intimal hyperplasia after vascular injury. Although MEK kinase 1 (MEKK1) has been shown to regulate cell migration and urokinase plasminogen activator (uPA) expression, the precise role of MEKK1 in this process remains unknown.

Methods and results

We triggered a vascular remodeling model by complete ligation of the right common carotid artery in wild-type (WT) and MEKK1-null (MEKK1-/-) mice. The intimal areas 28 days after ligation were significantly decreased in the ligated MEKK1-/-arteries compared with WT arteries (28+/-8 versus 65+/-17 microm2, P<0.05). There were no differences in the ratios of proliferating cell nuclear antigen (PCNA)-positive cells to total cells within the arterial wall between WT and MEKK1-/-arteries. Proliferation capacity also did not differ between WT and MEKK1-/-cultured aortic smooth muscle cells (AoSMCs). In contrast, the number of intimal PCNA-positive cells 7 days after ligation was significantly smaller in MEKK1-/-arteries. Three different migration assays revealed that migration and invasion of MEKK1-/-AoSMCs were markedly impaired. Addition of full-length MEKK1 restored the migration capacity of MEKK1-/- AoSMCs. The number of MEKK1-/-AoSMCs showing lamellipodia formation by epithelial growth factor was significantly smaller compared with those of WT SMCs. Furthermore, uPA expression after ligation was markedly decreased in MEKK1-/-arteries.

Conclusions

MEKK1 is implicated in vascular remodeling after blood-flow cessation by regulating the migration and uPA expression of SMCs. MEKK1 is a potential target for drug development to prevent vascular remodeling."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.org/dc/terms/identifier"doi:10.1161/01.cir.0000160350.20810.0f"xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Fujita M."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Minamino T."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Okada K."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Hirata A."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Hori M."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Takashima S."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Nagamachi Y."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Shintani Y."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Asanuma H."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Kitakaze M."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Tsukamoto O."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Johnson G.L."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Sanada S."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/author"Yujiri T."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/pages"1672-1678"xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/title"Ablation of MEK kinase 1 suppresses intimal hyperplasia by impairing smooth muscle cell migration and urokinase plasminogen activator expression in a mouse blood-flow cessation model."xsd:string
http://purl.uniprot.org/citations/15795331http://purl.uniprot.org/core/volume"111"xsd:string
http://purl.uniprot.org/citations/15795331http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15795331
http://purl.uniprot.org/citations/15795331http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15795331
▶