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Inhibitor TIMP-1 (inhibitor + timp-1)
Selected AbstractsEnhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential?INFLAMMATORY BOWEL DISEASES, Issue 11 2006Dr. Timo Rath PhD Abstract Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis. [source] Retinal pigment epithelial cells promote spatial reorganization and differentiation of retina photoreceptorsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2008Olga L. German Abstract Retina differentiation involves the acquisition of a precise layered arrangement, with RPE cells in the first layer in intimate contact with photoreceptors in the second layer. Here, we developed an in vitro coculture model, to test the hypothesis that RPE cells play a pivotal role in organizing the spatial structure of the retina. We cocultured rat retinal neurons with ARPE-19 epithelial cells under various experimental conditions. Strikingly, when seeded over RPE cells, photoreceptors attached to their apical surfaces and proceeded with their development, including the increased synthesis of rhodopsin. Conversely, when we seeded RPE cells over neurons, the RPE cells rapidly detached photoreceptors from their substrata and positioned themselves underneath, thus restoring the normal in vivo arrangement. Treatment with the metalloproteinase inhibitor TIMP-1 blocked this reorganization, suggesting the involvement of metalloproteinases in this process. Reorganization was highly selective for photoreceptors because 98% of photoreceptors but very few amacrine neurons were found to redistribute on top of RPE cells. Interestingly, RPE cells were much more efficient than other epithelial or nonepithelial cells in promoting this reorganization. RPE cells also promoted the growth of photoreceptor axons away from them. An additional factor that contributed to the distal arrangement of photoreceptor axons was the migration of photoreceptor cell bodies along their own neurites toward the RPE cells. Our results demonstrate that RPE and photoreceptor cells interact in vitro in very specific ways. They also show that in vitro studies may provide important insights into the process of pattern formation in the retina. © 2008 Wiley-Liss, Inc. [source] Matrix metalloproteinases MMP-7, MMP-9 and their tissue inhibitor TIMP-1: expression in chronic sinusitis vs nasal polyposisALLERGY, Issue 1 2004J. B. Watelet Background:, Nasal polyps (NP) are characterized by pseudocyst formation, whereas the mucosa in chronic sinusitis (CS) only shows a limited oedema. Matrix metalloproteinases (MMPs) are a family of endopeptidases able to degrade the extracellular matrix. Differences in histological features between CS and NP might be related to the respective expression of MMPs and their tissue inhibitors (TIMPs). Objective:, The aim of this study was to investigate MMP-7, MMP-9 and TIMP-1 proteins in NP and CS in comparison with normal mucosa. Methods:, Nasal samples, obtained from controls (n = 10), from NP (n = 8) and from CS (n = 10), were analysed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results:, In NP, compared with controls, staining for MMP-9 and MMP-7 appeared in blood vessels. Matrix metalloproteinase-9-positive inflammatory cells could be detected in increased numbers in pseudocyst formations. Concentrations of MMP-9 protein was found significantly increased in both CS and NP compared with controls, while MMP-7 was significantly increased in NP compared with controls and CS. Tissue inhibitors of metalloproteinase-1 protein was significantly increased in CS and NP when compared with controls. Conclusions:, Chronic sinusitis and NP show different pattern of MMP-7/-9 and TIMP-1 expression. We suggest that this difference in regulation of enzymes is related to the respective tissue remodelling observed in both diseases. [source] Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in the epithelium and stroma of salivary gland pleomorphic adenomasHISTOPATHOLOGY, Issue 3 2009Xiaojun Zhang Aims:, The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of normal salivary gland as well as in the mechanisms of tumour invasion and metastasis. The role of MMPs and TIMPs in pleomorphic adenoma has not been elucidated sufficiently. Our aim was to analyse the mRNA and protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the epithelium and stroma of pleomorphic adenoma and to evaluate their roles. Methods and results:, In each sample from six patients, cells from the epithelium and stroma were obtained by laser microdissection. The mRNA expression of MMPs and TIMPs was determined by real-time quantitative reverse transcriptase-polymerase chain reaction and protein expression was confirmed by immunohistochemistry. Results showed that mRNA expression of MMPs and TIMPs was significantly higher in stroma than in epithelium in most patients. MMPs and TIMPs were immunoreactive mainly in epithelium rather than in stroma. Conclusions:, Our results provide preliminary evidence that stromal myoepithelium may be the primary source of MMPs and that the stroma has the potential to play a more important role than ductal epithelium in biological behaviour of pleomorphic adenomas. These findings seem worthy of further investigation. [source] Effect of the anti-tumor necrosis factor-, antibody infliximab on the ex vivo mucosal matrix metalloproteinase,proteolytic phenotype in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Martin J. Meijer MSc Abstract Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-, antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by IBD versus control intestinal mucosa ex vivo and to assess the regulatory capacity by infliximab of the proteolytic phenotype. Methods: Intestinal mucosal explants from 20 IBD and 15 control patients were cultured with or without infliximab and/or the T-cell activator pokeweed mitogen (PWM). Explants and culture supernatants were analyzed for MMPs, TIMPs, and TNF-, protein, activity and/or mRNA levels. All patients were genotyped for functional TNF-,, MMP, and TIMP single nucleotide polymorphism (SNP) loci. Results: Expression of MMP and TIMP protein/activity in basal medium was higher in IBD versus control explants. Dependent on genotype at SNP loci, infliximab downregulated MMP-1, -3, and -9 relative to TIMP-1 and -2 and also decreased MMP-1 and -3 activities, while PWM enhanced these levels, partly counteracted again by infliximab. The expression of MMP-2 relative to TIMP did not change by treatment with infliximab and/or PWM. Conclusions: The high expression of MMPs in patients with IBD suggests a role for these proteinases in the pathogenesis of this disease. Infliximab seems to induce a genotype-associated matrix protective phenotype, which may contribute to the observed therapeutic efficacy of this drug in IBD, particularly at the mucosal surface. (Inflamm Bowel Dis 2007) [source] Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2009Martina Montagnana Abstract Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases involved in remodeling and physiological homeostasis of extracellular matrix (ECM). The metalloproteinases activity is predominantly modulated by specific tissue inhibitors of matrix metalloproteinases (TIMPs). The balance between MMPs and TIMPs is likely to play an important role in remodeling uterine arteries in pregnancy, and it may represent means by which vasodilatation is maintained in later pregnancy. Moreover, increased levels of MMPs and in particular MMP-2 play a role in the vascular alterations induced by hypertension. The aim of this study was the evaluation of MMP-2 and -9, along with their inhibitors TIMP-1 and -2, in pre-eclamptic women compared with normotensive pregnancy and non-pregnant women. Fourteen pre-eclamptic women were compared with 37 normotensive women in different gestational age and 21 non-pregnant women. Multiplexed sandwich enzyme-linked immunosorbent assay was used to measure MMPs and TIMPs simultaneously. MMP-2 levels were significantly higher in pre-eclamptic women vs. both non-pregnant and physiologic pregnant women. MMP-9 concentrations were significantly higher in physiologic pregnant vs. non-pregnant women. The serum levels of TIMP-1 were significantly higher in pre-eclamptic vs. both non-pregnant and physiologic pregnant women. TIMP-2 values were higher in physiologic pregnant women and pre-eclamptic women vs. non-pregnant women. A positive correlation between MMP-9 values and gestational age was observed in normal pregnant women. Results of the present investigation confirm that MMP-2 and TIMP-1 values are significantly higher in preeclampsia. We confirm that the modification of the fine balance between MMPs and their inhibitors plays a greater role in the structural and functional vascular changes of women with complicated pregnancies. J. Clin. Lab. Anal. 23:88,92, 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||