Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.17 (
MMP-3
)
3,419
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The matrix metalloproteinases (MMPs) are a family of endoproteinases that degrade various components of the extracellular matrix and have been implicated in the pathogenesis of multiple sclerosis. To determine whether up-regulation of
MMP-3
, or
stromelysin
-1, was a causative factor during the development of demyelination, we have examined the expression of
MMP-3
mRNA and protein in brain tissue of a spontaneously demyelinating mouse model overexpressing DM20 (
ND4
line) prior to and during the progression of disease. Stromelysin-1, but not other MMP mRNA was elevated approximately 10-fold in transgenic mice between 5 days and 1 month of age, more than 2 months before the onset of disease, and was coordinately expressed with the DM20 transgene. Stromelysin-1 protein levels were also up-regulated as was tissue inhibitor of metalloproteinase-1 (TIMP-1), an in vivo regulator of
stromelysin
-1 mRNA. When we crossed our
ND4
mice with a line of transgenic mice overexpressing TIMP-1 in brain, clinical signs in these mice were attenuated, and the level of
stromelysin
-1 protein was reduced. Thus, in this transgenic model of demyelinating disease up-regulation of DM20,
MMP-3
, and TIMP-1 represent important changes in the chemical pathogenesis in brain, which precede the onset of disease.
...
PMID:The up-regulation of stromelysin-1 (MMP-3) in a spontaneously demyelinating transgenic mouse precedes onset of disease. 1183 May 84
