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 iso-forms 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.

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis / Trentini, Alessandro; Manfrinato, Maria C.; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A.; Baldi, Eleonora; Tola, Maria R.; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico; Ferraro, Diana; Bedin, Roberta. - In: MULTIPLE SCLEROSIS. - ISSN 1352-4585. - 21:9(2015), pp. 1121-1130. [10.1177/1352458514560925]

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis

GRANIERI, ENRICO;Ferraro, Diana;Bedin, Roberta
2015

Abstract

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 iso-forms 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.
2015
6-feb-2015
21
9
1121
1130
TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis / Trentini, Alessandro; Manfrinato, Maria C.; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A.; Baldi, Eleonora; Tola, Maria R.; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico; Ferraro, Diana; Bedin, Roberta. - In: MULTIPLE SCLEROSIS. - ISSN 1352-4585. - 21:9(2015), pp. 1121-1130. [10.1177/1352458514560925]
Trentini, Alessandro; Manfrinato, Maria C.; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A.; Baldi, Eleonora; Tola, Maria R.; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico; Ferraro, Diana; Bedin, Roberta
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1141963
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