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1.
Gene ; 542(1): 38-45, 2014 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-24630964

RESUMO

Osteoarthritis (OA) is characterized by remodeling and degradation of joint tissues. Microarray studies have led to a better understanding of the molecular changes that occur in tissues affected by conditions such as OA; however, such analyses are limited to the identification of a list of genes with altered transcript expression, usually at a single time point during disease progression. While these lists have identified many novel genes that are altered during the disease process, they are unable to identify perturbed relationships between genes and gene products. In this work, we have integrated a time course gene expression dataset with network analysis to gain a better systems level understanding of the early events that occur during the development of OA in a mouse model. The subnetworks that were enriched at one or more of the time points examined (2, 4, 8, and 16 weeks after induction of OA) contained genes from several pathways proposed to be important to the OA process, including the extracellular matrix-receptor interaction and the focal adhesion pathways and the Wnt, Hedgehog and TGF-ß signaling pathways. The genes within the subnetworks were most active at the 2 and 4 week time points and included genes not previously studied in the OA process. A unique pathway, riboflavin metabolism, was active at the 4 week time point. These results suggest that the incorporation of network-type analyses along with time series microarray data will lead to advancements in our understanding of complex diseases such as OA at a systems level, and may provide novel insights into the pathways and processes involved in disease pathogenesis.


Assuntos
Artrite Experimental/genética , Articulações/patologia , Redes e Vias Metabólicas/genética , Osteoartrite/genética , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Modelos Animais de Doenças , Progressão da Doença , Adesões Focais/genética , Adesões Focais/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Articulações/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Osteoartrite/metabolismo , Osteoartrite/patologia , Receptores de Citoadesina/genética , Receptores de Citoadesina/metabolismo , Riboflavina/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/genética , Via de Sinalização Wnt/genética
2.
BMC Genomics ; 15: 59, 2014 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-24450868

RESUMO

BACKGROUND: Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. RESULTS: In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. CONCLUSIONS: The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.


Assuntos
Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica , Linfonodos/metabolismo , Scrapie/fisiopatologia , Ovinos/genética , Ovinos/metabolismo , Animais , Análise por Conglomerados , Regulação para Baixo , Adesões Focais/genética , Análise de Sequência com Séries de Oligonucleotídeos , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Príons/genética , Príons/metabolismo , Receptores de Citoadesina/genética , Receptores de Citoadesina/metabolismo , Scrapie/metabolismo , Scrapie/patologia , Regulação para Cima
3.
Head Neck ; 34(12): 1789-97, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22179951

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most common type of carcinoma worldwide. The pathogenic pathways involved in this cancer are mostly unknown; therefore, a better characterization of the OSCC gene expression profile would represent a considerable advance. The public availability of gene expression datasets was meant to obtain new insights on biological processes. METHODS: We integrated 4 public microarray datasets on OSCC to evaluate the degree of consistency among the biological results obtained in these different studies and to identify common regulatory pathways that could be responsible for tumor growth. RESULTS: Twelve altered cellular pathways implicated in OSCC and 4 genes altered in the extracellular matrix (ECM) receptor pathway were validated by quantitative real-time polymerase chain reaction (qRT-PCR). CONCLUSION: Using 4 expression array datasets, we have developed a robust method for analyzing pathways altered in OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Bases de Dados de Ácidos Nucleicos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/fisiopatologia , Bases de Dados Genéticas , Matriz Extracelular/genética , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Neoplasias Bucais/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Citoadesina/fisiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço
4.
Immunology ; 129(2): 248-56, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19824923

RESUMO

We previously showed alterations in the thymus during experimental infection with Plasmodium berghei. Such alterations comprised histological changes, with loss of cortical-medullary limits, and the intrathymic presence of parasites. As the combination of chemokines, adhesion molecules and extracellular matrix (ECM) is critical to appropriate thymocyte development, we analysed the thymic expression of ECM ligands and receptors, as well as chemokines and their respective receptors during the experimental P. berghei infection. Increased expression of ECM components was observed in thymi from infected mice. In contrast, down-regulated surface expression of fibronectin and laminin receptors was observed in thymocytes from these animals. Moreover, in thymi from infected mice there was increased CXCL12 and CXCR4, and a decreased expression of CCL25 and CCR9. An altered thymocyte migration towards ECM elements and chemokines was seen when the thymi from infected mice were analysed. Evaluation of ex vivo migration patterns of CD4/CD8-defined thymocyte subpopulations revealed that double-negative (DN), and CD4(+) and CD8(+) single-positive (SP) cells from P. berghei-infected mice have higher migratory responses compared with controls. Interestingly, increased numbers of DN and SP subpopulations were found in the spleens of infected mice. Overall, we show that the thymic atrophy observed in P. berghei-infected mice is accompanied by thymic microenvironmental changes that comprise altered expression of thymocyte migration-related molecules of the ECM and chemokine protein families, which in turn can alter the thymocyte migration pattern. These thymic disturbances may have consequences for the control of the immune response against this protozoan.


Assuntos
Movimento Celular/imunologia , Malária/imunologia , Plasmodium berghei/imunologia , Células Precursoras de Linfócitos T/metabolismo , Timo/metabolismo , Animais , Antígenos CD4/biossíntese , Antígenos CD8/biossíntese , Células Cultivadas , Quimiocinas/biossíntese , Quimiocinas/genética , Quimiocinas/imunologia , Regulação da Expressão Gênica , Malária/parasitologia , Malária/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Plasmodium berghei/patogenicidade , Células Precursoras de Linfócitos T/imunologia , Células Precursoras de Linfócitos T/parasitologia , Células Precursoras de Linfócitos T/patologia , Receptores de Citoadesina/biossíntese , Receptores de Citoadesina/genética , Receptores de Citoadesina/imunologia , Receptores de Fibronectina/biossíntese , Receptores de Fibronectina/genética , Receptores de Fibronectina/imunologia , Receptores de Laminina/biossíntese , Receptores de Laminina/genética , Receptores de Laminina/imunologia , Timo/imunologia , Timo/parasitologia , Timo/patologia
5.
Biophys J ; 96(9): 3555-72, 2009 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-19413961

RESUMO

We present a model that provides a mechanistic understanding of the processes that govern the formation of the earliest integrin adhesions ex novo from an approximately planar plasma membrane. Using an analytic analysis of the free energy of a dynamically deformable membrane containing freely diffusing receptors molecules and long repeller molecules that inhibit integrins from binding with ligands on the extracellular matrix, we predict that a coalescence of polymerizing actin filaments can deform the membrane toward the extracellular matrix and facilitate integrin binding. Monte Carlo simulations of this system show that thermally induced membrane fluctuations can either zip-up and increase the radius of a nucleated adhesion or unzip and shrink an adhesion, but the fluctuations cannot bend the ventral membrane to nucleate an adhesion. To distinguish this integrin adhesion from more mature adhesions, we refer to this early adhesion as a nouveau adhesion.


Assuntos
Adesão Celular , Membrana Celular/metabolismo , Integrinas/metabolismo , Modelos Biológicos , Receptores de Citoadesina/metabolismo , Actinas/metabolismo , Algoritmos , Membrana Celular/química , Simulação por Computador , Citoplasma/metabolismo , Matriz Extracelular/metabolismo , Método de Monte Carlo , Temperatura , Termodinâmica
6.
J Heart Lung Transplant ; 27(1): 38-45, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18187085

RESUMO

BACKGROUND: Circulating procoagulant microparticles are reliable markers of vascular damage. The microparticle phenotypes provide additional information reflecting the nature of cell injury. This study assessed procoagulant microparticle levels and phenotypes in the diagnosis of acute allograft rejection after heart transplantation. METHODS: Microparticles were prospectively investigated in the venous blood of 64 heart transplant patients, 23 with allograft rejection mainly of low score, and 41 without a rejection episode. Plasma concentrations of cytokines, cytoadhesins, and platelet activation markers were determined. RESULTS: By univariate analysis, the mean time elapsed from heart transplant, cold ischemia time, E-selectin-, Fas- and tissue factor-bearing microparticles were associated with allograft rejection. By multivariate analysis, E-selectin-microparticle levels appeared independently associated with allograft rejection, even when other significant variables were included in the model (odds ratio, 9.8; 95% confidence interval, 1.36-71.4; p = 0.023). CONCLUSION: The pattern of procoagulant microparticles released during acute allograft rejection suggests endothelial cell activation and Fas-mediated apoptosis. E-selectin-bearing microparticles appeared as an independent marker of acute allograft rejection that was still informative after adjustment for graft characteristics.


Assuntos
Selectina E/sangue , Endotélio Vascular/metabolismo , Rejeição de Enxerto/sangue , Transplante de Coração , Ativação Plaquetária/fisiologia , Tromboplastina/metabolismo , Receptor fas/sangue , Doença Aguda , Apoptose , Biomarcadores/sangue , Biópsia , Citocinas/sangue , Endotélio Vascular/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Rejeição de Enxerto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores de Citoadesina/sangue , Transplante Homólogo , Ultracentrifugação
7.
Pediatr Med Chir ; 29(1): 32-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17557508

RESUMO

OBJECTIVES: The Dystrophin-Glycoprotein Complex (DGC) is a large multisubunit complex that plays a crucial role in maintaining the structural integrity and physiology of muscle fibers. Dystrophin has been reported to be absent in the pyloric muscle of infantile hypertrophic pyloric stenosis (IHPS) patients. The present study was designed to investigate the other two patterns of DGC (dystroglycan and sarcoglycan complexes) in normal pyloric muscle and their possible modifications in IHPS patients. METHODS: Ten pyloric muscle biopsies were obtained from babies operated for IHPS and five control pylorus biopsy taken at autopsy from cases without gastrointestinal disease. The DGC sub-complexes (beta-dystroglican and beta, delta- sarcoglycans) were localized immunohistochemically using specific monoclonal antibodies. The results were evaluated using a confocal laser scanning microscope. RESULTS: Positive immunolocalization of the two DGC sub complexes was demonstrated in the smooth muscle cells (SMCs) of the pyloric region of control patients. Similarly, a positive immune expression of beta-dystroglican was observed in the pyloric SMCs of IHPS patients. On the other hand a negative immunoreaction for sarcoglycans was recorded within the full thickness of the pyloric SMCs of these patients. CONCLUSIONS: The absence of sarcoglycans within the hypertrophied pyloric muscle may be a predisposing factor in the pathogenesis of IHPS since it could alter the normal physiology of SMCs through the modifications of structural integrity of sarcolemma and signaling between the extracellular and intracellular compartment.


Assuntos
Estenose Pilórica Hipertrófica/imunologia , Estenose Pilórica Hipertrófica/patologia , Sarcoglicanas/imunologia , Biópsia , Distroglicanas/imunologia , Distroglicanas/metabolismo , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Microscopia Confocal , Fibras Musculares Esqueléticas/imunologia , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Estenose Pilórica Hipertrófica/metabolismo , Receptores de Citoadesina/imunologia , Receptores de Citoadesina/metabolismo
8.
Pediatr Dev Pathol ; 9(6): 427-43, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17163796

RESUMO

Over the past decade, molecular understanding of the congenital muscular dystrophies (CMDs) has greatly expanded. The diseases can be classified into 3 major groups based on the affected genes and the location of their expressed protein: abnormalities of extracellular matrix proteins (LAMA2, COL6A1, COL6A2, COL6A3), abnormalities of membrane receptors for the extracellular matrix (fukutin, POMGnT1, POMT1, POMT2, FKRP, LARGE, and ITGA7), and abnormal endoplasmic reticulum protein (SEPN1). The diseases begin in the perinatal period or shortly thereafter. A specific diagnosis can be challenging because the muscle pathology is usually not distinctive. Immunostaining of muscle using a battery of antibodies can help define a disorder that will need confirmation by gene testing. In muscle diseases with overlapping pathological features, such as CMD, careful attention to the clinical clues (e.g., family history, central nervous system features) can help guide the battery of immunostains necessary to target an unequivocal diagnosis.


Assuntos
Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Membrana/genética , Proteínas Musculares/genética , Distrofias Musculares/congênito , Distrofias Musculares/genética , Selenoproteínas/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Distrofias Musculares/diagnóstico , Mutação , Receptores de Citoadesina/genética , Receptores de Citoadesina/metabolismo , Selenoproteínas/metabolismo
9.
Virus Res ; 104(2): 145-55, 2004 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15246652

RESUMO

HIV-1-infected patients exhibit severe damages of the aortic endothelium, develop angioproliferative lesions such as Kaposi's sarcoma (KS), and have an increased risk of cardiovascular diseases and atherosclerosis. An increased adhesion of leukocytes to the endothelium is a common pathogenic parameter of AIDS-associated vascular diseases. Here we show that the HIV-1 Tat protein, a regulatory protein of HIV-1 released by infected cells, and TNF-alpha, a cytokine increased in sera and tissues of HIV-1-infected patients, activate synergistically the adhesion of leukocytes to endothelial cells both in vitro and in vivo. This effect is selectively mediated by HIV-1 Tat, since HIV-1 Nef, another HIV-1 regulatory protein, and the HIV-1 envelope protein gp41, had no effect. In vitro adhesion assays with PBMC and quantitative cell type analysis of adherent cells by FACS demonstrated that HIV-1 Tat selectively activates the adhesion of T-cells and monocytes but not of B-cells. Intravital microscopic studies in mice confirmed the synergistic activity of HIV-1 Tat and TNF-alpha on leukocyte adhesion to the endothelium in vivo. These data indicate that HIV-1 Tat in cooperation with TNF-alpha may contribute to the vascular damage and cardiovascular diseases observed in AIDS patients but also to the prominent extravasation of T-cells and monocytes which is a key process in the formation and progression of KS lesions.


Assuntos
Adesão Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Produtos do Gene tat/farmacologia , HIV-1/química , Monócitos/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Adesão Celular/fisiologia , Agregação Celular , Células Cultivadas , Endotélio Vascular/imunologia , Produtos do Gene tat/imunologia , Humanos , Técnicas In Vitro , Monócitos/imunologia , RNA Mensageiro , Receptores de Citoadesina/metabolismo , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana
10.
Ageing Res Rev ; 3(2): 233-47, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15177057

RESUMO

Extracellular matrix (ECM) has been a central topic in aging research for several years. Cell-matrix interactions extend the interest in this topic both for normal tissue homeostatic regulation as well as for its dysregulation in age-related diseases. A relatively new extension of this ever-increasing field of aging research concerns the recognition of the original biological activities exhibited by proteolytic fragments of matrix macromolecules. A number of such matricryptins were recently identified, some of them endowed with harmful effects for tissue function. Some of the breakdown products exert a positive feedback effect by upregulating the biosynthesis of the original macromolecule synthesis and/or the expression of degrading enzymes. This results in vicious circles which might well be involved in tissue aging. The examples detailed in this review concern fibronectin (FN) and elastin. A number of fibronectin fragments (Fn-fr) were shown to exhibit diverse activities including increasing tissue degradation, inflammation and tumor progression. Elastin degradation products acting as agonists on the elastin-laminin receptor can trigger harmful effects such as up-regulation of proteases and free radical production. Both macromolecules are at the center of autoamplifying vicious circles of potential importance for age-dependent modification of tissue function.


Assuntos
Envelhecimento/fisiologia , Comunicação Celular/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Integrina alfa5beta1/fisiologia , Animais , Humanos , Receptores de Superfície Celular/fisiologia , Receptores de Citoadesina/fisiologia
11.
Eur J Immunol ; 33(9): 2439-48, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12938220

RESUMO

Several T cell abnormalities have been described in the course of acute Trypanosoma cruzi infection in mice, including severe effects on the thymus. In the present study, looking at the expression of extracellular matrix ligands in the thymus, we observed that deposits of fibronectin and laminin increased progressively during the course of infection, reaching a maximum at the peak of parasitemia and thymic atrophy. Concomitantly, membrane expression of fibronectin and laminin receptors (VLA-4, VLA-5 and VLA-6) was also enhanced on thymocyte subsets of infected mice. These results correlated with changes in intrathymic thymocyte migration ability during the acute phase of infection, when a higher fibronectin-dependent transmigratory activity of CD4(+)CD8(+) thymocytes was observed. Strikingly, we detected higher frequency of immature and high VLA-expressing CD4(+)CD8(+) T cells in the peripheral lymphoid organs of infected mice at the peak of parasitemia. These cells seemed to be thymus dependent, since significantly lower amounts of them were found in thymectomized mice, and some of them carry "prohibited" Vbeta segments of the TCR. Our data suggest an imbalance in the intrathymic cell trafficking following acute T. cruzi infection, likely due to dysregulated extracellular matrix-dependent interactions.


Assuntos
Movimento Celular/fisiologia , Doença de Chagas/metabolismo , Timo/metabolismo , Trypanosoma cruzi/patogenicidade , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Matriz Extracelular/metabolismo , Camundongos , Receptores de Citoadesina/biossíntese , Receptores de Citoadesina/genética
13.
Clin Immunol ; 104(1): 67-72, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12139949

RESUMO

We have previously demonstrated by immunohistochemistry that mucosal expression of beta 2 integrins was enhanced in Crohn's disease and ulcerative colitis as compared to normal controls. We aimed, therefore, to determine whether there was a corresponding alteration in the expression of CD11a/CD18 (LFA-1), the primary lymphocyte beta 2 integrin, among the principal subsets of lamina propria lymphocytes (LPLs). Accordingly, LPLs were extracted from surgical resection specimens derived from patients with Crohn's colitis, ulcerative colitis, and from noninflamed controls. Following immunofluorescent staining, three-color flow-cytometry analysis identified LPLs on the basis of CD45 side scatter gating, which in turn, were further subdivided into CD4(+), CD8(+), and CD19(+) cells to account for the predominant T and B cells in the lamina propria. Expression patterns of CD11a, the alpha-subunit of LFA-1; CD18, the beta-subunit of LFA-1; and alpha d, a novel alpha-subunit of the beta 2 integrin family were assessed for each of these lymphocyte subsets. In Crohn's disease and ulcerative colitis there was an increased mean percentage expression of CD4(+) cells and CD11a(+) cells compared with noninflamed controls. CD11a was more likely to be expressed on CD4(+) cells in both Crohn's disease and ulcerative colitis and compared with controls and less expressed on CD19(+) cells. It is likely that an influx of CD4(+)11a(+) cells into the lamina propria accounted for these changes. These results suggest that although currently there is great interest in harnessing alpha 4 beta 7 in treatment of inflammatory bowel disease, further consideration should be given to the role of CD11a in these disease states.


Assuntos
Antígenos CD18/biossíntese , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Integrinas/biossíntese , Antígeno-1 Associado à Função Linfocitária/biossíntese , Receptores de Citoadesina , Antígenos CD19/imunologia , Antígenos CD11 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Colo/citologia , Colo/imunologia , Colo/patologia , Humanos , Cadeias alfa de Integrinas , Subpopulações de Linfócitos T/imunologia
14.
Curr Opin Genet Dev ; 12(3): 320-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12076676

RESUMO

Lissencephaly, which means 'smooth cortex', is caused by defective neuronal migration during development of the cerebral cortex and has devastating clinical consequences. 'Classical' lissencephaly seems to reflect mutations in regulators of the microtubule cytoskeleton, whereas 'cobblestone' lissencephaly is caused by mutations in genes needed for the integrity of the basal lamina of the central nervous system. Reelin, which is mutated in a third type of lissencephaly, may represent a unifying link because it encodes an extracellular protein that regulates neuronal migration and may also regulate the microtubule cytoskeleton.


Assuntos
Proteínas Associadas aos Microtúbulos/genética , Neocórtex/embriologia , Neuropeptídeos/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase , Animais , Membrana Basal/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas do Domínio Duplacortina , Matriz Extracelular/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Proteínas de Membrana , Microtúbulos/genética , Microtúbulos/metabolismo , N-Acetilglucosaminiltransferases/genética , Proteínas do Tecido Nervoso , Proteínas/genética , Receptores de Citoadesina/metabolismo , Proteína Reelina , Serina Endopeptidases , Transdução de Sinais
15.
Int J Oral Maxillofac Implants ; 17(6): 771-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12507235

RESUMO

PURPOSE: Initial adhesion of cells to implant surfaces and subsequent behavior of the cells are important determinants for biocompatibility of the implants. It was previously reported that both adhesion of MC3T3-E1 osteoblast-ike cells to titanium (Ti) plates and their differentiation into more mature cells on the plates were stimulated by treatment of the plates with glow discharge plasma (GDP). However, the mechanisms of these processes have not yet been identified. In this study, the adhesion and differentiation mechanism of osteoblast-like cells to Ti with and without GDP were investigated. MATERIALS AND METHODS: The adhesion and differentiation mechanism of MC3T3-E1 osteoblast-like cells to Ti, with and without GDP, were investigated by cultivation in serum-free medium and use of a competitive inhibition test to examine the influence of extracellular matrix proteins contained in the serum and to identify cell binding proteins. In addition, the amount of fibronectin adsorption on each Ti plate was investigated by enzyme-linked immunosorbent assay and fluorescein isothiocyanate labeling. Furthermore, the stress fiber formation and morphology of cells on each plate were evaluated microscopically. RESULTS: Adherent cells on Ti plates, with and without GDP, were significantly reduced in serum-free conditions and the presence of RGDS (Arg-Gly-Asp-Ser) peptides. Fibronectin adsorption on titanium plates was increased by GDP. Furthermore, stress fiber formation of cells was extremely progressive on the Ti plates treated with GDP and was not observed on the cells inhibited by RGDS peptide. DISCUSSION: These results suggest that RGDS containing serum proteins have a major role in regulating specific adhesion of cells to Ti, and GDP promoted cell adhesion and differentiation on Ti by increasing the adsorption of proteins. CONCLUSION: According to this study, the adhesion and differentiation mechanism of osteoblast-like cells to Ti, with and without GDP, can be obtained.


Assuntos
Adesão Celular , Materiais Revestidos Biocompatíveis , Osteoblastos/fisiologia , Receptores de Citoadesina/fisiologia , Titânio , Argônio , Ligação Competitiva , Proteínas Sanguíneas/fisiologia , Diferenciação Celular , Células Cultivadas , Meios de Cultura Livres de Soro/química , Eletrólise , Ensaio de Imunoadsorção Enzimática , Fibronectinas/análise , Fibronectinas/fisiologia , Fluoresceínas , Oligopeptídeos/fisiologia , Ligação Proteica , Propriedades de Superfície
16.
Microbiology (Reading) ; 147(Pt 11): 3159-64, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11700367

RESUMO

It has been hypothesized that Candida albicans possesses integrin-like receptors on its cell surface. This is because C. albicans binds numerous fluid-phase extracellular matrix (ECM) proteins on its cell surface and adheres to the same ECM proteins when immobilized. In addition, numerous antibodies to human integrins (receptors for ECM proteins) bind to the fungal cell surface and in so doing inhibit the binding of the respective proteins. To demonstrate the presence of such a cell surface integrin, a cDNA library of C. albicans yeast cells was screened with polyclonal antiserum to the human fibronectin receptor (alpha5beta1 integrin). Clones isolated by this screening technique also reacted specifically to antiserum against the human vitronectin receptor (alpha(v)beta3 integrin). DNA sequence analysis of the cloned insert predicted a 350 aa protein (37 kDa). This predicted protein showed 75% homology at the nucleotide sequence level to alcohol dehydrogenase (ADH) of Saccharomyces cerevisiae. In vitro transcription/translation of the cloned inserts yielded a 37 kDa protein that was immunoprecipitated with antibodies to the alpha5beta1 and alpha(v)beta3 integrins and an antibody to a C. albicans fibronectin receptor. These antibodies and an mAb to the human vitronectin receptor demonstrated an antigen of -37 kDa present in the cell-wall preparations of C. albicans and in spent growth medium. All four antibodies reacted with authentic ADH. The possible significance of these results in relation to C. albicans adherence is discussed.


Assuntos
Álcool Desidrogenase/imunologia , Anticorpos Antibacterianos/imunologia , Candida albicans/enzimologia , Candida albicans/imunologia , Receptores de Fibronectina/imunologia , Receptores de Vitronectina/imunologia , Saccharomyces cerevisiae/genética , Álcool Desidrogenase/genética , Anticorpos Monoclonais/imunologia , Candida albicans/metabolismo , Candida albicans/ultraestrutura , Adesão Celular , Parede Celular/fisiologia , Clonagem Molecular , Reações Cruzadas , Escherichia coli , Biblioteca Gênica , Humanos , Ligação Proteica , Receptores de Citoadesina/análise , Receptores de Citoadesina/metabolismo , Saccharomyces cerevisiae/fisiologia
17.
J Dent Res ; 80(6): 1540-4, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11499509

RESUMO

Integrin adhesion and signaling events may contribute to the progressive differentiation of the osteoblast and to the initiation of a mineralized matrix. The purpose of our study was to begin to analyze the role of integrin receptors, in particular alpha2beta1, alpha5beta1, and alphaVbeta3, regarding mediation of the initiation of a mineralized matrix. Integrin-perturbation assays were conducted in microdot cultures of UMR-106-01 Bone Sialoprotein (BSP) osteoblast cells. For phenotypic analysis, we performed bright-field microscopy and Aliziran Red S staining to analyze effects on mineralization initiation. Mineralization was reduced significantly (P < 0.001) following the addition of alpha5- or beta1-integrin subunit antibody by approximately 20% and 45%, respectively--alphaVbeta3 integrin by nearly 65%, and alpha2beta1 integrin by nearly 95%. This effect was reversible following the removal of the antiintegrin antibody. These results suggest that integrin adhesion and signaling events may contribute to the ability of this cell line to mediate the initiation of the mineralization phenotype biologically.


Assuntos
Adesão Celular/fisiologia , Osteoblastos/metabolismo , Receptores de Citoadesina/metabolismo , Calcificação de Dente/fisiologia , Análise de Variância , Animais , Diferenciação Celular , Relação Dose-Resposta Imunológica , Matriz Extracelular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Sialoproteína de Ligação à Integrina , Integrinas/metabolismo , Osteossarcoma/metabolismo , Ligação Proteica/fisiologia , Ratos , Receptores de Colágeno , Receptores de Fibronectina/metabolismo , Receptores de Vitronectina/metabolismo , Sialoglicoproteínas/fisiologia , Transdução de Sinais , Calcificação de Dente/genética , Células Tumorais Cultivadas
18.
Wiad Parazytol ; 47(4): 573-8, 2001.
Artigo em Polonês | MEDLINE | ID: mdl-16886392

RESUMO

Cerebral malaria in man and in animals is the consequence of a cascade of events, involving the patological changes, leading to the amplification of the expression of the receptors for cytoadherence on brain capillary endothelial cells. Sequestration is the process by which erytrocytes infected with the mature forms of the malaria parasite Plasmodium falciparum disappear from circulation and accumulate within venules and capillaries of various organs and tissues. The molecular mechanism in sequestration is one of the most rapidly advancing fields in malaria research. The several specific aspects considered in this paper. Our electron micrographs show cytoadherence in own model of cerebral malaria in rats infected with Plasmodium berghei.


Assuntos
Adesão Celular , Endotélio Vascular/ultraestrutura , Eritrócitos/patologia , Malária Cerebral/patologia , Malária Cerebral/parasitologia , Animais , Encéfalo/irrigação sanguínea , Capilares , Moléculas de Adesão Celular/ultraestrutura , Eritrócitos/ultraestrutura , Interações Hospedeiro-Parasita , Camundongos , Plasmodium berghei , Ratos , Receptores de Citoadesina/ultraestrutura
19.
Exp Neurol ; 166(1): 52-64, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11031083

RESUMO

The inflammatory response that ensues during the initial 48 to 72 h after spinal cord injury causes considerable secondary damage to neurons and glia. Infiltration of proinflammatory-activated neutrophils and monocytes/macrophages into the cord contributes to spinal cord injury-associated secondary damage. beta2 integrins play an essential role in leukocyte trafficking and activation and arbitrate cell-cell interactions during inflammation. The beta2 integrin, alphaDbeta2, is expressed on monocytes/macrophages and neutrophils and binds to vascular adhesion molecule-1 (VCAM-1). The increased expression of VCAM-1 during central nervous system (CNS) inflammation likely contributes to leukocyte extravasation into the CNS. Accordingly, blocking the interaction between alphaDbeta2 and VCAM-1 may attenuate the inflammatory response at the SCI site. We investigated whether the administration of monoclonal antibodies (mAbs) specific for the rat alphaD subunit would reduce the inflammatory response after a spinal cord transection injury in rats. At a 1 mg/kg dose two of three anti-alphaD mAbs caused a significant ( approximately 65%) reduction in the number of macrophages at the injury site and one anti-alphaD mAb led to a approximately 43% reduction in the number of neutrophils at the SCI site. Thus, our results support the concept that the alphaDbeta2 integrins play an important role in the trafficking of leukocytes to a site of central nervous system inflammation. This study also offers preliminary evidence that anti-alphaD mAbs can reduce the extravasation of macrophages and, to a lesser extent, neutrophils, to the SCI site.


Assuntos
Movimento Celular/imunologia , Integrinas/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Mielite/terapia , Receptores de Citoadesina , Traumatismos da Medula Espinal/terapia , Animais , Antígenos CD11 , Modelos Animais de Doenças , Cadeias alfa de Integrinas , Integrinas/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Metilprednisolona/farmacologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Mielite/imunologia , Mielite/fisiopatologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/fisiopatologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
20.
Toxicon ; 38(6): 775-91, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10695965

RESUMO

In thrombosis, platelet aggregation is initiated by a specific membrane glycoprotein (GP) Ib-IX-V complex binding to its adhesive ligand, von Willebrand factor, in the matrix of ruptured atherosclerotic plaques or in plasma exposed to high hydrodynamic shear stress. This process closely resembles normal haemostasis at high shear, where GP Ib-IX-V-dependent platelet adhesion to von Willebrand factor in the injured blood vessel wall initiates platelet activation and integrin alphaIIb beta3 (GP IIb-IIIa)-dependent platelet aggregation. At low shear, other receptors such as those that bind collagen, the integrin alpha2beta1 (GP Ia-IIa) or GP VI, mediate platelet adhesion. Recently, snake venom proteins have been identified that selectively modulate platelet function, either promoting or inhibiting platelet aggregation by targeting GP Ib-IX-V, alpha2beta1, GP VI, alphaIIb beta3, or their respective ligands. Interestingly, these venom proteins typically belong to one of two major protein families, the C-type lectin family or the metalloproteinase-disintegrins. This review focuses on recent insights into structure-activity relationships of snake venom proteins that regulate platelet function, and the ways in which these novel probes have contributed in unexpected ways to our understanding of the molecular mechanisms underlying thrombosis.


Assuntos
Adesividade Plaquetária/efeitos dos fármacos , Venenos de Serpentes/toxicidade , Sequência de Aminoácidos , Animais , Antígenos CD36/metabolismo , Humanos , Ligantes , Dados de Sequência Molecular , Adesividade Plaquetária/fisiologia , Receptores de Citoadesina/metabolismo , Receptores de Trombina/metabolismo , Venenos de Serpentes/química , Relação Estrutura-Atividade , Fator de von Willebrand/metabolismo
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