MMP-9 and its relationship to disease activity


Trentini A, Manfrinato MC, Castellazzi M, Tamborino C, Roversi G, Volta CA, Baldi E, Tola MR, Granieri E, Dallocchio F, Bellini T, Fainardi E; the Emilia-Romagna network for Multiple Sclerosis(ERMES) study group. TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.
Mult Scler. 2015. pii: 1352458514560925. [Epub ahead of print]

BACKGROUND:The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown.
OBJECTIVE:To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis.
METHODS:We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls.
RESULTS:Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively).
CONCLUSION:Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.
Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase orgelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zincmetalloproteinases family involved in the degradation of the extracellular matrix. In humans the MMP9 gene. encodes for a signal peptide, a propeptide, a catalytic domain with inserted three repeats of fibronectin type II domain followed by a C-terminal hemopexin-like domain. It is associated with inflammation. TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms. This protein is a member of the TIMP family. The glycoprotein is a natural inhibitor of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In this study they looked at blood levels and found MMP-9 inparticular a TIMP-resistant foorm of MMP-9. These proteins can bemeasured by assays taking hours to do. I wonder if we could do this quicker?

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