Association of circulating levels of MMP-8 with mortality from respiratory disease in patients with rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA

Evaluation of Proanthocyanidin-based dentifrices on dentin-wear after erosion and dental abrasion - In situ study

Proanthocyanidin has been considered as a preventive agent against erosion because of its properties, which involves remineralization, reduction of demineralization and matrix metalloproteinases (MMPs) inhibition. Thus, the aim of this in situ study was

マトリックスメタロプロテアーゼと膵疾患

Matrix metalloproteinases (MMPs) is a family of collagenolytic enzymesand are associated with many pathological conditions. Especially, MMPs have a strong relation with tumor progression and invasion. In this review, we focused on association of MMPs and pancreatic diseases, and a potential treatment of MMPs inhibitors for pancreatic cancer.マトリックスメタロブロテアーゼ（MMP）は，コラーゲン分解能を有し，種々の疾患との関連性が示唆されている。とりわけ,癌の浸潤，転移には密接な関係があるとされている。また，MMP阻害剤を癌の治療に用いる試みもなされている。本稿ではMMPと膵疾患の関連性，MMP阻害剤の膵癌への応用の可能性について総説する

Multifaceted role of matrix metalloproteinases (MMPs)

Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc-containing endopeptidases, are involved in the tissue remodeling and degradation of the extracellular matrix. MMPs are widely distributed in the brain and regulate various processes including microglial activation, inflammation, dopaminergic apoptosis, blood-brain barrier disruption, and modulation of α-synuclein pathology. High expression of MMPs is well documented in various neurological disorders including Parkinson\u27s disease (PD), Alzheimer\u27s disease (AD), Japanese encephalitis (JE), and Glaucoma. Although potentially critical, the role of MMPs in neuronal disorders is under-investigated. The present review summarizes the role of MMPs in neurodegeneration with a particular emphasis on PD, AD, JE, and Glaucoma

Imbalances between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in maternal serum during preterm labor

Background: Matrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor. Methods: A case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology. Results: MMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor. Conclusions: Serum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition

Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha).

Matrix metalloproteinases (MMPs) have a crucial function in migration of inflammatory cells into the central nervous system (CNS). Levels of MMP-9 are elevated in multiple sclerosis (MS) and predict the occurrence of new active lesions on magnetic resonance imaging (MRI). This translational study aims to determine whether in vivo treatment with the pregnancy hormone estriol affects MMP-9 levels from immune cells in patients with MS and mice with experimental autoimmune encephalomyelitis (EAE). Peripheral blood mononuclear cells (PBMCs) collected from three female MS patients treated with estriol and splenocytes from EAE mice treated with estriol, estrogen receptor (ER) alpha ligand, ERbeta ligand or vehicle were stimulated ex vivo and analyzed for levels of MMP-9. Markers of CNS infiltration were assessed using MRI in patients and immunohistochemistry in mice. Supernatants from PBMCs obtained during estriol treatment in female MS patients showed significantly decreased MMP-9 compared with pretreatment. Decreases in MMP-9 coincided with a decrease in enhancing lesion volume on MRI. Estriol treatment of mice with EAE reduced MMP-9 in supernatants from autoantigen-stimulated splenocytes, coinciding with decreased CNS infiltration by T cells and monocytes. Experiments with selective ER ligands showed that this effect was mediated through ERalpha. In conclusion, estriol acting through ERalpha to reduce MMP-9 from immune cells is one mechanism potentially underlying the estriol-mediated reduction in enhancing lesions in MS and inflammatory lesions in EAE

Matrix metalloproteinases as target genes for gene regulatory networks driving molecular and cellular pathways related to a multistep pathogenesis of cerebrovascular disease

The present study investigated a joint contribution of matrix metalloproteinases (MMPs) genes to ischemic stroke (IS) development and analyzed interactions between MMP genes and genome‐wide associated loci for IS. A total of 1288 unrelated Russians (600 IS patients and 688 healthy individuals) from Central Russia were recruited for the stud

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

A study on the expression levels of matrix metalloproteinases and their inhibitors in patients with ulcerative colitis

Purpose: To investigate the expression matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ulcerative colitis (UC) patients admitted to The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.Methods: The expression of MMPs and TIMPs) was evaluated in 50 patients (36 males, 14 females) with UC who were admitted to The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. Tissue samples obtained from core needle biopsies were evaluated using immunochemistry techniques.Results: MMP-9 and TIMP-1 were strongly expressed in the glandular epithelium and inflammatory cells. In addition, the expression was coupled with changes in the tissue architecture and inflammation in the lamina propria. The expression of MMPs and weak activation of their inhibitors was related to UC progression. There were significant correlations between MMP expression and histopathological parameters (p = 0.051, R = 0.392). MMP expression correlated with weaker expression of TIMPs (p = 0.032, R = 0.0581)Conclusion: MMP-2, MMP-7, and MMP-9 are potential targets for therapeutic control of UC.Keywords: Glandular epithelium, Inflammatory cells, Inhibitors, Matrix  metalloproteinases (MMPs), Tissue inhibitors of metalloproteinases, Ulcerative coliti