RGD Reference Report - TIMP-4 is regulated by vascular injury in rats. - Rat Genome Database

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TIMP-4 is regulated by vascular injury in rats.

Authors: Dollery, CM  McEwan, JR  Wang, M  Sang, QA  Liu, YE  Shi, YE 
Citation: Dollery CM, etal., Circ Res. 1999 Mar 19;84(5):498-504.
RGD ID: 2290470
Pubmed: PMID:10082471   (View Abstract at PubMed)

The role of basement membrane-degrading matrix metalloproteinases (MMPs) in enabling vascular smooth muscle cell migration after vascular injury has been established in several animal models. In contrast, the role of their native inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), has remained unproven despite frequent coregulation of MMPs and TIMPs in other disease states. We have investigated the time course of expression and localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days, and 14 days after balloon injury by in situ hybridization, immunohistochemistry, and Western blot analysis. TIMP-4 protein was present in the adventitia of injured carotid arteries from 24 hours after injury. At 7 and 14 days after injury, widespread immunostaining for TIMP-4 was observed throughout the neointima, media, and adventitia of injured arteries. Western blot analysis confirmed the quantitative increase in TIMP-4 protein at 7 and 14 days. In situ hybridization detected increased expression of TIMP-4 as early as 24 hours after injury and a marked induction in neointimal cells 7 days after injury. We then studied the effect of TIMP-4 protein on the migration of smooth muscle cells through a matrix-coated membrane in vitro and demonstrated a 53% reduction in invasion of rat vascular smooth muscle cells. These data and the temporal relationship between the upregulation of TIMP-4, its accumulation, and the onset of collagen deposition suggest an important role for TIMP-4 in the proteolytic balance of the vasculature controlling both smooth muscle migration and collagen accumulation in the injured arterial wall.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Wounds and Injuries  ISOTimp4 (Rattus norvegicus)2290470; 2290470mRNA and protein:increased expression:carotid arteryRGD 
Wounds and Injuries  IEP 2290470mRNA and protein:increased expression:carotid arteryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Timp4  (TIMP metallopeptidase inhibitor 4)

Genes (Mus musculus)
Timp4  (tissue inhibitor of metalloproteinase 4)

Genes (Homo sapiens)
TIMP4  (TIMP metallopeptidase inhibitor 4)


Additional Information