RGD Reference Report - MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells.

Authors: Filippov, S  Koenig, GC  Chun, TH  Hotary, KB  Ota, I  Bugge, TH  Roberts, JD  Fay, WP  Birkedal-Hansen, H  Holmbeck, K  Sabeh, F  Allen, ED  Weiss, SJ 
Citation: Filippov S, etal., J Exp Med. 2005 Sep 5;202(5):663-71.
RGD ID: 1582575
Pubmed: PMID:16147977   (View Abstract at PubMed)
PMCID: PMC2212885   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20050607   (Journal Full-text)

During pathologic vessel remodeling, vascular smooth muscle cells (VSMCs) embedded within the collagen-rich matrix of the artery wall mobilize uncharacterized proteolytic systems to infiltrate the subendothelial space and generate neointimal lesions. Although the VSMC-derived serine proteinases, plasminogen activator and plasminogen, the cysteine proteinases, cathepsins L, S, and K, and the matrix metalloproteinases MMP-2 and MMP-9 have each been linked to pathologic matrix-remodeling states in vitro and in vivo, the role that these or other proteinases play in allowing VSMCs to negotiate the three-dimensional (3-D) cross-linked extracellular matrix of the arterial wall remains undefined. Herein, we demonstrate that VSMCs proteolytically remodel and invade collagenous barriers independently of plasmin, cathepsins L, S, or K, MMP-2, or MMP-9. Instead, we identify the membrane-anchored matrix metalloproteinase, MT1-MMP, as the key pericellular collagenolysin that controls the ability of VSMCs to degrade and infiltrate 3-D barriers of interstitial collagen, including the arterial wall. Furthermore, genetic deletion of the proteinase affords mice with a protected status against neointimal hyperplasia and lumen narrowing in vivo. These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
carotid stenosis  ISOMmp14 (Mus musculus)1582575; 1582575 RGD 
carotid stenosis  ISOMmp2 (Mus musculus)1582575; 1582575 RGD 
carotid stenosis  IAGP 1582575 RGD 
carotid stenosis  IEP 1582575 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp14  (matrix metallopeptidase 14)
Mmp2  (matrix metallopeptidase 2)

Genes (Mus musculus)
Mmp14  (matrix metallopeptidase 14 (membrane-inserted))
Mmp2  (matrix metallopeptidase 2)

Genes (Homo sapiens)
MMP14  (matrix metallopeptidase 14)
MMP2  (matrix metallopeptidase 2)


Additional Information