Increased expression ratio of matrix metalloproteinase-9 (MMP9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) RNA levels in Iranian multiple sclerosis patients
Affiliations: [a] Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Tonekabon, Iran | [b] Department of Medical Genetics, School of Medicine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [c] Department of Hematology, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [d] Department of Epidemiology and Biostatistics, Faculty of Health, Qom University of Medical Sciences, Qom, Iran | [e] GenoDive Pharma Inc., Atsugi, Japan
Correspondence:
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Corresponding author: Arezou Sayad, Department of Medical Genetics, School of Medicine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 1985717443, Tehran, Iran. Tel.: +98 21 23872572; Fax: +98 2123872572; E-mail:[email protected]
Note: [1] These authors contributed equally to this work.
Abstract: OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease
involving the central nervous system (CNS) with unknown immunopathogenic
mechanisms. Matrix metalloproteinase-9 (MMP-9) facilitates T-cell migration
into the CNS while the tissue inhibitor matrix metalloproteinase-1 (TIMP-1)
inhibits MMP-9 actions. The aim of this study was to evaluate the expression
of TIMP-1 RNA and MMP-9/TIMP-1 RNA ratio in blood cells of Iranian patients
with relapsing-remitting multiple sclerosis (RRMS) treated with IFNb. MATERIAL AND METHODS: The study compared the expression level of
TIMP-1 gene in RRMS samples with normal individuals in Iran and the results
were compared using a ratio of MMP-9 to TIMP-1. All patients were
HLA-DRB1*15 negative and were responders to interferon-beta with a normal
vitamin D level. RESULTS: The RRMS patients manifested a lower expression level of
TIMP-1 RNA than their normal counterparts although the result was not
significant (P= 0.06). Also, the ratio of MMP-9 to TIMP-1 RNA increased
significantly (P= 0.009). There was no linear correlation between TIMP-1
expression level and risk of Expanded Disability Status Scale of Kurtzke
(EDSS); nor was there any significant correlation between expression status
of TIMP-1 and duration of the disease. Although there was no significant
decrease in TIMP-1 expression level, the MMP-9/TIMP-1 RNA ratio in RRMS was
significantly higher than normal subjects. CONCLUSION: Further studies are recommended to compare MMP-9/TIMP-1
RNA ratio in patients before and after taking IFN-beta in order to find out
if MMP-9/TIMP-1 RNA ratio can function as a proper marker of the bio
efficacy of IFN-beta treatment of MS.
Keywords: MMP-9, TIMP-1, expression, multiple sclerosis, real time PCR
