Deteccão de diferentes microorganismos na periodontite crônica, da glicoproteína EMMPRIN (CD-147) e sua correlação com a produção de MMP-2 e MMP-9

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prostate hyperplasia caused by long-term obesity is characterized by high deposition of extracellular matrix and increased content of MMP-9 and VEGF

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long-term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high-fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α-actin, vimentin, chondroitin sulphate and metalloproteinases (MMP-2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione-S-Transferase (GST) were quantified by enzymatic assay. Long-term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α-actin and MMP-9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long-term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.

Detecção de Periodontopatógenos, Glicoproteína Emmprin (Cd-147) e sua correlação com MMP-2 e MMP-9

Periodontitis is an infectious disease characterized by the secretion of a variety of inflammatory mediators that lead to destruction of tooth supporting tissues, including the possible loss of alveolar bone, in association with infection with multiple species of bacteria. It is estimated that more than 400 species colonize the biofilm and some oral species related to periodontal disease is present in the subgingival including P. gingivalis, T. forsythia and T. denticola. However, other organisms may be related of this disease, as Filifactor allocis and Prevotella tannerae. These microorganisms and subproducts such as endotoxins released into the extracellular lead to the stimulation of metalloproteinase inducer glycoprotein (EMMPRIN, CD-147), which stimulates the release of MMPs by host cells, like fibroblasts and endothelial cells, thus leading to tissue destruction. The objective of this study was to detect F. allocis, P. tannerae, T. denticola and the glycoprotein EMMPRIN (CD-147) and its correlation with MMP-2 and MMP-9 in subgingival fluid samples of patients with chronic periodontitis. Fluids were collected from healthy and disease subgingival sites of 20 healthy individuals before basic periodontal treatment and after of 60 days of treatment. Their DNAs were extracted and portions of the 16S gene were amplified and performed conventional PCR. For immunological analysis and quantification of EMMPRIN (CD-147), MMP-2 and MMP-9 was used ELISA-Sandwich. Results demonstrated that the disease group showed significantly high amounts of T. denticola, F. alocis and P. tannerae when compared with health sites. MMP-2 and MMP-9 were detected in high concentrations with statistically significantly reduction after periodontal treatment to MMP-2, but without correlation with EMMPRIN.

Expressão imuno-histoquímica de KI-67, COX-2, MMP-9 e P53 nos tumores testiculares caninos

Pós-graduação em Ciência Animal - FMVA

Ketorolac eye drops reduce inflammation and delay re-epithelization in response to corneal alkali burn in rabbits, without affecting iNOS or MMP-9

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunoexpression of ROCK-1 and MMP-9 as prognostic markers in breast cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression in the prostatic tissue of two ethanol-preferring rat models

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

In vitro effect of caffeic acid phenethyl ester on matrix metalloproteinases (MMP-1 and MMP-9) and their inhibitor (TIMP-1) in lipopolysaccharide-activated human monocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Immunohistochemical detection of metalloproteinase-9 (MMP-9), anti-oxidant like 1 protein (AOP-1) and synaptosomal-associated protein (SNAP-25) in the cerebella of dogs naturally infected with spontaneous canine distemper

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Functional Polymorphism Located in MMP-9 Gene Promoter Is Strongly Associated with Obesity

The adipose tissue expansion is accompanied by remodeling of extracellular matrix performed by matrix metalloproteinases (MMPs). Higher plasma and tissue MMP-9 levels are found in obese; therefore, we evaluated if the functional C-1562T polymorphism (rs3918242) located in promoter region of the MMP-9 gene is associated with obesity in women. We studied 112 lean and 114 obese women. Plasma MMP-9 and tissue inhibitor of MMP-9 (TIMP)-1 were measured using enzyme-linked immunosorbent assay. We found different genotype frequencies between lean and obese women (p = 0.008), prevailing T-allele in obese (2.3-fold). However, although obese women present higher levels of plasma MMP-9, lack of modulation by the polymorphism was found (all p > 0.05). Our findings suggest that C-1562T polymorphism may contribute to pathogenetic mechanisms involved in the development of obesity in women.

Genetic Variants in Matrix Metalloproteinase-9 Gene Modify Metalloproteinase-9 Levels in Black Subjects

Altered matrix metalloproteinases (MMPs) levels are involved in cardiovascular diseases and increased MMP-9 levels enhance the cardiovascular risk in apparently healthy subjects. We investigated the effects of MMP-9 gene polymorphisms and haplotypes on the circulating MMP-9 levels in healthy black subjects and the effects of an MMP-2 polymorphism on the plasma MMP-2 concentrations. We studied 190 healthy subjects, nonsmokers, self-reported as blacks (18-63 years). Genotypes for the MMP-2 C-1306T polymorphism and the MMP-9 C-1562T, 90(CA)(14-24) and Q279R polymorphisms (rs243865, rs3918242, rs2234681, and rs17576, respectively) were determined by TaqMan (R) Allele Discrimination assay and real-time polymerase chain reaction or restriction fragment length polymorphism. Alleles for the 90(CA)(14-24) polymorphism were grouped as low (L) when there were < 21 and high (H) when there were >= 21 CA repeats. The plasma levels of MMP-2 and MMP-9 were determined by gelatin zymography. The software PHASE 2.1 was used to estimate the haplotypes frequencies. Although we found no effects of the MMP-9 C-1562T or the Q279R polymorphisms on MMP-9 levels, higher MMP-9 levels were associated with the HH genotype for the -90(CA)(14-24) polymorphism compared with the HL or LL genotypes. Lower MMP-9 levels were found in carriers of the CRL haplotype (combining the C, R, and L alleles for the MMP-9 polymorphisms) compared with the CRH haplotype. Consistent with this finding, the CRL haplotype was more commonly found in subjects with low MMP-9 levels. The MMP-2 C-1306T polymorphism had no effects on the plasma MMP-2 levels. Our results show that MMP-9 genetic variations modify MMP-9 levels in black subjects and may offer biochemical evidence implicating MMP-9 in the pathogenesis of cardiovascular diseases in blacks.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women

Objectives: To compare the plasma concentrations of matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1, MMP-8, and myeloperoxidase (MPO) for obese and lean women. Design and methods: We recruited 30 lean and 36 obese women without comorbidities. The MMP-9, TIMP-1, and MMP-8 levels were measured using enzyme-linked immunosorbent assay (ELISA). MPO activity was assessed by a colorimetric assay. Results: Obese women had higher MMP-9 levels and MMP-9:TIMP-1 ratios than lean women. Conversely, the MMP-8 levels and MMP-8:TIMP-1 ratios in the obese women were significantly lower than those in the lean women despite neutrophil activation, which was assessed by MPO activity., Conclusion: We observed that MMP-9 and MMP-8 had distinct profiles, which suggested that these 2 enzymes play different roles in obesity. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

Abstract Background Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components. Objectives To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue. Methods Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified. Results Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue. Conclusions MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.