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Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs.

ABSTRACT: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor.Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and specific TIMP-2 and TIMP-1, respectively, has been investigated in meningiomas of different grades.Selected formalin-fixed paraffin-embedded tissue from 43 meningiomas of dogs was evaluated.Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR).MMP-9 was not expressed in all of the tumors, but MMP-2 was significantly more expressed in papillary meningioma. Likewise, the MMP-2/TIMP-2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma, TIMP-1 gene expression was significantly higher than in grades I and III.MMP-2/TIMP-2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs. TIMP-1 expression may play a role independent of MMP-9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans.

SUBMITTER: Mandara MT

PROVIDER: S-EPMC5697205 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs.

Mandara M T MT Reginato A A Foiani G G De Luca S S Guelfi G G

Journal of veterinary internal medicine 20170905 6

<h4>Background</h4>Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor.<h4>Hypothesis/objectives</h4>Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and spe ...[more]

PMID: 28875568

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Project description:BackgroundMatrix 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.MethodsA 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.ResultsMMP-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.ConclusionsSerum 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.

Project description:IntroductionBovine papillomaviruses -1/-2 (BPVs) are small non-enveloped double-stranded DNA viruses able to infect the skin of bovids and equids, causing development of neoplastic lesions such as bovine cutaneous fibropapillomas and equine sarcoid. Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that degrade basal membrane and extracellular matrix, whose function is essential in physiological processes such as tissue remodeling and wound healing. MMPs activity is finely regulated by a balancing with expression of tissue inhibitors of MMPs (TIMPs), a process that is impaired during tumour development. BPV infection is associated with upregulation of MMPs and /or their unbalancing with TIMPs, contributing to local invasion and impairment of extracellular matrix remodeling in equine sarcoid; however, studies regarding this topic in bovine fibropapillomas are lacking.MethodsThe aim of this study was to perform an immunohistochemical and biochemical analysis on a panel of MMPs and TIMPs in BPV-2 positive bovine cutaneous fibropapillomas vs. normal skin samples.ResultsImmunohistochemistry revealed a cytoplasmic expression of MMP-2 (15/19), a cytoplasmic and perinuclear immunoreactivity of MMP-7 (19/19) and MMP-9 (19/19), along with a cytoplasmic and nuclear pattern of MMP-14 (16/19), accompanied by a cytoplasmic expression of TIMP-1 (14/19) and TIMP-2 (18/19) in tumour samples; western blotting revealed an overexpression of MMP-2 (8/9), MMP-7 (9/9) and MMP-9 (9/9), and a decreased level of MMP-14 (9/9), TIMP-1 (9/9) and TIMP-2 (9/9) in tumour versus normal skin samples. Moreover, gelatine zymography confirmed the expression of pro-active MMP-2 (9/9) and MMP-9 (9/9) and, most importantly, indicated the presence and increased activity of their active forms (82 and 62 kDa, respectively) in tumour samples.DiscussionThis is the first study describing MMPs and TIMPs in bovine cutaneous fibropapillomas and our results suggest that their unbalanced expression in presence of BPV-2 may play a significant role in tumour development. A further analysis of supplementary MMPs and TIMPs could bring new important insights into the papillomavirus induced tumours.

Project description:ObjectiveTurnover of cartilage endplate extracellular matrix (ECM) may play an important role in disc degeneration and low back pain (LBP). However, the expression pattern of pro-inflammatory factors, matrix metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) in the cartilage endplates (CEP) of intervertebral discs (IVD) is not understood. We aimed to examine the transcriptional levels of MMP, TIMP, and interleukins (IL), and the correlations between them.MethodsThirty degenerated cartilage endplate samples from patients with LBP who underwent lumbar fusion surgery were included in the degenerated group. Ten patients without LBP history who underwent lumbar surgery because of vertebral burst fractures were included in the control group. The degenerative severity of the samples was evaluated by MRI, and hematoxylin-eosin and safranin O-fast green (SO-FG) staining. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3, IL-1α, IL-1β, and IL-6. The correlations between the levels of these genes were tested using Spearman's rho test.ResultsHematoxylin-eosin and SO-FG staining confirmed a decrease in cell number and proteoglycans in the degenerated cartilage endplate. MRI showed significant signal changes in degenerated cartilage endplates. Patients in the degenerated group showed a higher rate of endplate Modic changes when compared with the control group. MMP-3, MMP-9, TIMP-3, IL-1α, and IL-1β were elevated with statistical significance, while MMP-1, MMP-13, TIMP-1, TIMP-2, and IL-6 were changed without statistical significance or remained unchanged. Expression of MMP-3 was positively correlated with IL-1α (Spearman coefficient, 0.486; P < 0.05); expression of TIMP-3 was positively correlated with MMP-9, IL-1α, and IL-1β (Spearman coefficient, 0.577, 0.407, and 0.571, respectively; P < 0.05).ConclusionMMP-3, MMP-9, TIMP-3, IL-1α, and IL-1β may play a role in the process of cartilage endplate degeneration. MMP-3 may be regulated by IL-1α, and TIMP-3 might be associated with MMP-9 and regulated by IL-1α and IL-1β.

Project description:Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and indicative of cardiac amyloid disease type.Fifty AL-CMP patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR patients). Clinical and laboratory evaluations including echocardiography were performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP), troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP-2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR, 1.041; P<0.01) were predictors for mortality for all patients with cardiac amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090; P<0.01). There were no prognostic factors for all-cause death in TTR-CMP patients.Circulating concentrations of MMPs and TIMPs may be useful in differentiating patients with AL-CMP from those with TTR-CMP, resulting in earlier diagnostic vigilance, and may add prognostic information. In addition to an elevated BNP level, female sex increased the risk of death in patients with cardiac amyloidoses.

Dataset Information

Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs.

Publications

Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs.

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