| First Author | D'Souza CA | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 16 | Pages | 13589-96 |
| PubMed ID | 11830584 | Mgi Jnum | J:76052 |
| Mgi Id | MGI:2178465 | Doi | 10.1074/jbc.M108817200 |
| Citation | D'Souza CA, et al. (2002) The Up-regulation of Stromelysin-1 (MMP-3) in a Spontaneously Demyelinating Transgenic Mouse Precedes Onset of Disease. J Biol Chem 277(16):13589-96 |
| abstractText | 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. |
