Matrix metalloproteinases and their pathological upregulation in multiple sclerosis: an overview

Javaid, Muhammad; Abdallah, Mohamed‐Nur; Ahmed, Ahad S.; Sheikh, Zeeshan

doi:10.1007/s13760-013-0239-x

Cited by 30 publications

(26 citation statements)

References 65 publications

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“…The second mechanism is activation of inactive forms of certain inflammation mediators by increased levels of MMPs. Breakdown of the myelin sheath within the CNS parenchyma by MMPs results in demyelination and inflammation within the CNS (19). The release of MMPs at the sites of inflammation and their role in degradation of the various components of the extracellular matrix (19,20) indicates that the genetic variants of MMPs might affect the function of MMP enzymes.…”

Section: Discussionmentioning

confidence: 99%

The Association Between Matrix Metalloproteinase-7 A-181G Polymorphism and the Risk of Relapsing-Remitting Multiple Sclerosis in Iranian Kurdish Patients from Kermanshah

Mohammadi¹,

Rahimi²,

Rahimi³

2015

Avicenna J Med Biochem

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Background: Multiple sclerosis (MS) is a common chronic genetic disease of the central nervous system. The relapsing-remitting-MS (RR-MS) is the most common form of this disease. Matrix metalloproteinase-7 (MMP-7) is an important member of the MMP family, which degrades many extracellular matrix components. The common polymorphism of MMP-7 A-181G is associated with some diseases. Objectives: The aim of the present study was to determine the influence of this polymorphism on the risk of RR-MS. Materials and Methods: Eighty RR-MS patients and 80 healthy individuals as controls from the Kermanshah province were studied for MMP-7 A-181G polymorphism by using the PCR-RFLP method. Data were analyzed using the SPSS statistical software package version 16.0. Results: In RR-MS patients the frequency of MMP-7 GG genotype was significantly (P = 0.028) higher compared to that of the controls. The presence of GG genotype increased the risk of RR-MS by 1.69 times [OR = 1.69 and 95% CI = 1.05-2.72, P = 0.03]. The frequency of MMP-7 G allele in RR-MS patients was significantly higher (51.2%, P = 0.043) than that of the controls (40%). The presence of this allele increased the risk of RR-MS by 1.58 folds (P = 0.044). Conclusions: Our findings indicate that the presence of G allele of MMP-7 A-181G polymorphism might increase the risk of RR-MS in our population.

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Section: Discussionmentioning

confidence: 99%

The Association Between Matrix Metalloproteinase-7 A-181G Polymorphism and the Risk of Relapsing-Remitting Multiple Sclerosis in Iranian Kurdish Patients from Kermanshah

Mohammadi¹,

Rahimi²,

Rahimi³

2015

Avicenna J Med Biochem

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“…In adults, the majority of remaining MMP activity is isolated to remodeling processes such as wound repair and angiogenesis. However, in human disease, aberrant MMP hyperactivity has been observed in many pathological conditions, such as osteoarthritis, multiple sclerosis, and cancer 2,42…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

Roy

Walsh

2014

BCTT

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The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.

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“…Matrix metalloproteinases (MMP) constitute a large group of proteolytic enzymes involved in degrading and remodeling the extracellular matrix. In order to alter the extracellular matrix, MMP must modify (activate or inactivate) a variety of soluble or membrane‐bound proteins, which can occur in normal physiological and pathological conditions, such as multiple sclerosis and atherosclerosis . It has been shown that different cell types, such as lymphocytes, macrophages and glial cells, produce MMP, and these enzymes play important roles in the pathogenesis of inflammatory diseases of the central nervous system (CNS) .…”

Section: Introductionmentioning

confidence: 99%

“…In order to alter the extracellular matrix, MMP must modify (activate or inactivate) a variety of soluble or membrane-bound proteins, which can occur in normal physiological and pathological conditions, such as multiple sclerosis and atherosclerosis. [1][2][3][4] It has been shown that different cell types, such as lymphocytes, macrophages and glial cells, produce MMP, and these enzymes play important roles in the pathogenesis of inflammatory diseases of the central nervous system (CNS). [1][2][3][4] For example, in multiple sclerosis (MS), MMP might contribute to the migration of immune cells into the CNS from the bloodstream through proteolytic disruption of the subendothelial basement membrane of the blood-brain barrier (BBB).…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] It has been shown that different cell types, such as lymphocytes, macrophages and glial cells, produce MMP, and these enzymes play important roles in the pathogenesis of inflammatory diseases of the central nervous system (CNS). [1][2][3][4] For example, in multiple sclerosis (MS), MMP might contribute to the migration of immune cells into the CNS from the bloodstream through proteolytic disruption of the subendothelial basement membrane of the blood-brain barrier (BBB). 5 Of the various MMP, MMP-9 has been reported to increase in both the serum and cerebrospinal fluid (CSF) of patients with MS, and is recognized as a candidate marker of MS disease activity.…”

Section: Introductionmentioning

confidence: 99%

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Human immunoglobulin G suppresses the production of matrix metalloproteinase‐9 in peripheral blood mononuclear cells of patients with multiple sclerosis

Okada

2015

Clinical & Exp Neuroim

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Objective Matrix metalloproteinase (MMP)-9 is a key molecule that indicates disruption of the blood-brain barrier (BBB), and is recognized as a candidate biomarker of disease activity in multiple sclerosis (MS). The aim of the present study was to determine whether human immunoglobulin G (hIgG) could reduce the production of MMP-9 in peripheral blood mononuclear cells (PBMC) from patients with MS. Methods We investigated the effect of hIgG on the expression of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in PBMC of patients with relapsing-remitting MS (RRMS) compared with healthy controls (HC) in vitro. Results Patients with RRMS were not receiving any disease-modifying therapies when blood was sampled in this study. Although levels of MMP-9 and TIMP-1 in PBMC were not different between RRMS and HC groups, the MMP-9/TIMP-1 ratio was significantly increased in patients with RRMS when compared with HC. PBMC that were stimulated with lipopolysaccharide (LPS, 1 lg/mL) expressed a higher level of MMP-9 in RRMS than the HC groups, although the level of TIMP-1 was equal between groups. hIgG reduced the level of MMP-9 in PBMC from both patients with RRMS and HC with LPS stimulation in a dose-dependent manner, but had no effect on the expression of TIMP-1. The MMP-9/TIMP-1 ratio in both patients with RRMS and HC was also decreased by hIgG. The effect of hIgG was not through neutralization of MMP-9. hIgG alone did not induce MMP-9 mRNA, and suppressed the upregulation of mRNA in PBMC stimulated with LPS. Conclusions These results suggest that hIgG could be effective in treating patients with RRMS though the inhibition of the transmigration of immune cells into the brain parenchyma.

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Matrix metalloproteinases and their pathological upregulation in multiple sclerosis: an overview

Cited by 30 publications

References 65 publications

The Association Between Matrix Metalloproteinase-7 A-181G Polymorphism and the Risk of Relapsing-Remitting Multiple Sclerosis in Iranian Kurdish Patients from Kermanshah

The Association Between Matrix Metalloproteinase-7 A-181G Polymorphism and the Risk of Relapsing-Remitting Multiple Sclerosis in Iranian Kurdish Patients from Kermanshah

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

Human immunoglobulin G suppresses the production of matrix metalloproteinase‐9 in peripheral blood mononuclear cells of patients with multiple sclerosis

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