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The role of connective tissue growth factor (ctgf) in oval cell aided liver regeneration in the 2-aaf/phx modelPi, Liya, January 2005 (has links)
Thesis (Ph.D.)--University of Florida, 2005. / Typescript. Title from title page of source document. Document formatted into pages; contains 162 pages. Includes Vita. Includes bibliographical references.
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La migration des microglies et les molécules adhésives au cours du développement embryonnaire du cerveau / Microglial migration and adhesion molecules during embryonic brain developmentSmolders, Sophie 30 October 2017 (has links)
Les microglies sont des cellules hématogène mais prennent place dans le système nerveux central (SNC) au cours du développement embryonnaire pour constituer la population résidente des cellules immunitaires. Elles sont les médiateurs crucials du bon développement et de l'entretien des réseaux de neurones dans le SNC. De nombreux aspects de la physiologie microgliale et les mécanismes qui sous-tendent leurs fonctions au cours du développement embryonnaire du cerveau sont encore largement méconnues. Cette thèse de doctorat porte sur la migration des cellules microgliales au cours du développement embryonnaire du cortex et elle débouche sur trois grandes conclusions. (1) Les cellules microgliales embryonnaires in situ sont très dynamiques et adaptent leur phénotype à leur environnement local. (2) La vitesse de migration des microglies ex vivo dépend des intégrines beta1 qui exercent des fonctions à la fois inhibitrices et promotrices sur la migration selon l'âge embryonnaire. (3) Les microglies jouent probablement un rôle dans l'étiologie des troubles du développement neurologique, mais il faudrait que les futures recherches se concentrent sur le dysfonctionnement des microglies plutôt que sur leur activation immunitaire classique. / Microglia are blood-borne cells but take up residence in the central nervous system (CNS) during embryonic development to constitute the resident pool of immune cells. They are crucial mediators of the healthy development and maintenance of neural networks in the CNS. Many aspects of the physiology of microglia and the mechanisms underpinning their tasks during embryonic brain development are still unresolved. This doctoral dissertation focuses on migration of microglial cells during embryonic cortical development. All together, this dissertation brings forwards three major conclusions. (1) In situ embryonic microglia are highly dynamic cells that adapt their phenotype to their local environment. (2) Microglial migration speed ex vivo is dependent on β1 integrins that exert both migration promoting and inhibiting functions which are age-specifically regulated. (3) Microglia likely play a role in the etiology of neurodevelopmental disorders, but further research should focus on microglia dysfunction rather than classical microglial immune activation.
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Reproduction in vitro d'un intestin sur puce microfluidique / In vitro reproduction of a gut on a microfluidic chipVerhulsel, Marine 01 October 2015 (has links)
L’épithélium intestinal est composé d’une monocouche de cellules épithéliales qui recouvrent à la fois les villi qui projettent dans le lumen et les cryptes invaginées dans le tissu conjonctif sous-jacent. Les cellules souches intestinales prolifèrent dans les cryptes et se différencient en 5 types de cellules différenciées incluant les entérocytes, les cellules de Paneth, les cellules caliciformes, les cellules entéroendocrines et les cellules Tuft. La plupart de ces cellules différenciées migrent vers le pôle apical du villus où elles meurent par apoptose exception faite des cellules de Paneth qui sont présentes uniquement dans les cryptes. Les cellules épithéliales adhèrent à la membrane basale qui sépare l’épithélium du stroma principalement constitué de collagène I et de fibroblastes. L’épithélium intestinal est renouvelé chaque semaine. Plusieurs voies de signalisation biochimiques qui gouvernent l’homéostasie intestinale ont été isolées en utilisant des modèles murins. En complément des études menées in vivo, des systèmes in vitro ont été développés de répondre à des questions difficiles à étudier in vivo, on peut notamment citer les organoides. Malgré leur indiscutable intérêt, les organoides ne reproduisent pas certaines caractéristiques majeures de l’intestin, à savoir que le nombre de total de cellules ne reste pas constant, qu’ils ne forment pas spontanément des villi et que le stroma est absent de ces modèles. Présentement, uniquement deux microsystèmes ont tenté de pallier l’absence de villi de ces modèles en reproduisant des caractéristiques dynamique (i.e le mouvement péristaltique) ou architecturale (i.e la topographie des villi) de l’intestin dans le but d’induire la formation des villi. Cependant, dans ces deux systèmes, les cellules ne reposent pas sur un substrat physiologique et sont directement ensemencées sur un support élastomérique. Quand bien même la surface de ces substrats est traitée avec des molécules constitutives de la matrice extracellulaire (ECM), ils ne reproduisent pas la micro-architecture (e.g sa structure microfibrillaire et la possibilité d’être remodelée par les cellules ensemencées) et les propriétés mécaniques spécifiques de l’ECM intestinale. Il est ainsi fort probable que ces systèmes induisent des phénotypes différents de ceux comprenant un substrat physiologique. Pour éviter ces phénomènes, nous avons développé un système innovant qui reproduit à la fois la composition et la topographie de la matrice intestinale. Le collagène I, en tant que principal composant des matrices extracellulaires, des mammifères a naturellement été choisi comme substrat cellulaire. La composition ainsi que les propriétés rhéologiques du collagène commercial ont été comparées au collagène extrait de queue de rat dans le laboratoire. Les techniques de lithographies ont été adaptées pour microstructurer les hydrogels en collagène en une sinusoïde tridimensionnelle de 400µm de période et 400µm d’amplitude en accord avec les dimensions anatomiques des intestins de souris. Les cellules épithéliales de lignées Caco2 qui sont considérées comme un modèle de cellules intestinales ont été ensemencées à la surface de la structure et ont colonisé les micro-structures en formant une monocouche cellulaire. L’utilisation du collagène I permet l’inclusion de fibroblastes primaires dans la matrice où ils évoluent in vivo. Les forces de tension développées par la monocouche épithéliale à la surface de la matrice mais également par les fibroblastes dans l’hydrogel affaissent les structures. Plus la concentration en collagène des gels est importante moins les structures sont déformées. Cependant, pour des concentrations supérieures à 6mg/mL, les fibroblastes présentent des difficultés pour s’étaler et proliférer dans la matrice probablement dues à une diffusion réduite des nutriments dans de telles matrices mais également à une réduction de la taille du maillage fibrillaire qui empêche l’étalement des cellules. / The epithelium of the small intestine is composed of a single layer of epithelial cells lining the villi that project into the lumen of the gut, and the crypts that descend into the underlying connective tissue. Dividing stem cells are contained within the crypts and give rise to five types of specialized epithelial cells including enterocytes, Goblet cells, Paneth cells, enteroendocrine cells and Tuft cells. Most of those cells travel upwards from the crypt towards the villus tip where they shed into the lumen except for Paneth cells that remain confined into the crypt. The basement membrane underlines the basal surface of epithelium and separates it from the stroma mostly composed of collagen I and fibroblasts. The whole intestinal epithelium is renewed every week. Many biochemical pathways that control intestinal homeostasis are discovered using mouse models. In contrast, in vitro models systems, such as organoids, provide a mean to investigate questions hard to be addressed in vivo. Despite their obvious interest, organoids do not fully recapitulate intestinal features: the total number of cells does not remain constant, villi-like structures are missing as well as cells and matrix constitutive of the stroma. Only two microfabricated devices have been developed to overcome this absence of villi by replicating dynamic (i.e the peristaltic motion) or structural feature (i.e the topography of the villus) of the intestine in order to induce the formation of villi. However they both do not provide the cells a physiological substrate as cells are directly seeded on an elastomeric synthetic scaffold. Even though those substrates are coated with ECM molecules, as they miss the micro-architecture specific of ECM (e.g. fibrillar structure and capacity to be remodeled by cells) as well as their mechanical properties; they might induce a different phenotype to the cells than if they were seeded on/in an ECM-like hydrogel. To address this lack, we developed an innovative device that recapitulates both the composition and topography of the intestinal lining. We chose collagen I as the constituent of our substrate since collagen I is the most abundant protein in mammals and the main constituent of all ECM in the body. We first characterized the composition and the rheological properties of commercial rat tail collagen I hydrogel and compared it to the one we extracted from rat tails. To reproduce the 3D structure of the intestine, we microstructured collagen I scaffolds as 3D sinusoids with 400µm period and 400µm height that respect the anatomic dimensions of mice intestine by adapting methods from soft lithography field. Epithelial cells from Caco2 cell line which are considered as an intestinal model were first seeded on the surface of the scaffold and successfully colonized the structure as a monolayer. Primary fibroblasts were embedded in collagen scaffolds were they actually belong in vivo. The force exterted by the epithelial monolayer at the surface of the scaffold but also by the fibroblasts inside the gels flattened the structures. The higher the concentration of collagen was the less the structures were deformed. However, for collagen concentrations higher than 6mg/mL, the fibroblasts experienced difficulties to spread and proliferate in the matrix probably related to a reduced diffusion of nutrients in such matrix or to the reduced mesh size of the fibrillar network that prevent cell spreading. Two main approaches were investigated to stiffen the collagen scaffold while maintaining a porosity suitable for fibroblasts spreading and proliferation. One consisted in the addition of a stiffer biocompatible polymer to generate a hybrid semi-interpenetrating network hydrogel with improved mechanical properties. The other resided in the addition of a cross-linker that covalently bonded the fibrils constitutive of the collagen network.
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O papel dos proteoglicanos na adesão celular durante a tumorigênese: um modelo in vitro para o estudo da interação câncer-estroma / The Role of proteoglycans on cell adhesion during tumorigenesis: a model to study tumor-stroma interactions in vitroVicente, Carolina Meloni [UNIFESP] 27 May 2009 (has links) (PDF)
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Previous issue date: 2009-05-27 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Fundo de Auxílio aos Docentes e Alunos (FADA) / Durante a metastase, as celulas perdem seu contato tecidual original, movem-se pela matriz extracelular (MEC), invadem o sistema linfatico e/ou sanguineo, extravasam e formam novos tumores. Devido a isso, essas celulas tumorais precisam modificar sua adesao celula-MEC. Receptores de adesao exercem papeis cruciais na transformacao neoplasica de celulas normais atraves da inducao de comportamentos celulares e morfologicos especificos do cancer. Isto implica que celulas tumorais provavelmente expressam e utilizam um conjunto distinto de receptores de adesao celular durante e carcinogenese. Sindecam-2 e um proteoglicano transmembranico de heparam sulfato (HS) que participa da formacao de dominios especializados na membrana plasmatica e funciona diretamente como um vinculo entre o ambiente extracelular e a organizacao do citoplasma cortical. Em diversas linhagens celulares de cancer colorretal, a expressao de sindecam-2 encontra-se aumentada, quando comparada com linhagens normais, e este aumento parece ser critico para o comportamento das celulas cancerosas, uma vez que regula sua adesao e proliferacao, e, portanto, sua atividade tumorigenica. Os resultados obtidos neste trabalho demonstraram que em celulas de carcinoma colorretal altamente metastaticas, pertencentes a linhagem HCT-116, a expressao e a sintese de sindecam-2 sao intensificadas na presenca de MEC produzida por fibroblastos. Os demais sindecans sofrem diminuicao, assim como o HS presente na MEC produzida pelas celulas tumorais. Entre os componentes da MEC estromal, a fibronectina mostrou-se como principal responsavel pelo aumento de sindecam-2. Houve co-localizacao entre sindecam-2, integrina ƒÑ5ƒÒ1 e fibronectina, o que sugere a participacao destas moleculas no mecanismo de adesao em celulas HCT-116. Alem disso, o bloqueio de sindecam-2 resultou na nao formacao de fibras de estresse durante a adesao celular, indicando seu importante papel na regulacao de filamentos de actina. Fica claro, portanto, o papel fundamental da MEC estromal na regulacao da expressao de proteinas de superficie celular e provavelmente na sinalizacao para o interior de celulas cancerosas, modificando sua proliferacao, adesao e seu formato. / During metastasis cells lose their original tissue contacts, move through the extracellular matrix (ECM), enter the lymphatic and/or blood system, extravasate and subsequently form new tumors. Therefore, these tumor cells must experience changes in cell-ECM adhesion. Adhesion receptors play crucial roles in the neoplastic transformation of normal cells through the induction of cancer-specific cellular behavior and morphology. This implies that cancer cells likely express and utilize a distinct set of adhesion receptors during carcinogenesis. Syndecan-2 is a transmembrane heparan sulfate (HS) proteoglycan which has been implicated in the formation of specialized membrane domains and functions as a direct link between the extracellular environment and the organization of the cortical cytoplasm. In several colon-rectal cancer cell lines, syndecan-2 is highly expressed compared to normal cell lines. This increase appears to be critical for cancerous cell behavior since it regulates adhesion and proliferation and therefore the tumorigenic activity. The results of this study showed that in a highly metastatic colon-rectal cancer cell line, HCT-116, both expression and synthesis of syndecan-2 are enhanced when grown on ECM produced by fibroblasts. The expression of the others syndecans decreased, as did HS in the ECM produced by the cancer cells. Among the stromal components of ECM, the fibronectin was shown to be important for the increase of syndecan-2. Co-localization between syndecan-2, integrin ƒÑ5ƒÒ1 and fibronectin, suggests the involvement of these molecules in the adhesion mechanism of HCT-116 cells. Furthermore, blocking syndecan-2 with an antibody resulted in the absence of stress fibers during cell adhesion, indicating its important role in the regulation of actin filaments. Thus, the stromal ECM has a fundamental role in regulating the expression of cell surface proteins and probably signaling to the interior of cancer cells by altering their proliferation and adhesion, and its format. / TEDE / BV UNIFESP: Teses e dissertações
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Modelagem matemática da propagação do câncerVilla, Julio César Nuñez January 2015 (has links)
Orientador: Prof. Dr. Norberto Anibal Maidana / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Matemática , 2015. / Neste trabalho propomos um modelo matemático para estudar a proliferação e a
propagação tumoral no tecido hospedeiro. Modelamos o processo mediante um sistema
de três equações diferenciais, descrevendo a interação entre as células tumorais, a
matriz extracelular e as enzimas degradadoras da matriz extracelular. Inicialmente,
descrevemos a produção (ou a ativação) das enzimas de degradação pelas células
cancerígenas, assim como seu decaimento, a degradação e a remodelação da matriz
extracelular e o crescimento celular. No modelo espacial, consideramos a dispersão
por difusão das células tumorais e das enzimas degradadoras, considerando também
a resposta migratória das células tumorais à matriz extracelular, haptotaxia. Fazemos
um estudo da dinâmica temporal mediante seus pontos de equilíbrio e a estabilidade,
obtendo uma classificação qualitativa.
Simulações numéricas são analisadas e interpretadas biologicamente. Nas simulações
espaciais, em dimensão um, obtemos a formação de uma frente de onda, para a
qual analisamos a velocidade, as mudanças de velocidades em alguns cenários e as
implicações biológicas destas variações. / In this work, we propose a mathematical model to study the proliferation and tumor
spread in a host tissue. We model the process using three differential equations, describing
the interaction between tumor cells, the extracellular matrix and the degrading
enzymes of the extracellular matrix. At first, we describe the production (or activation)
of degradative enzymes by the cancer cells as well as its decay, the degradation and
remodeling of the extracellular matrix and cell growth. Then, in the spatial model, we
consider the dispersion by diffusion of tumor cells and of the degradative enzymes, as
well as the migratory response of tumor cells to the extracelular matrix, haptotaxia.
We make a study of the temporal dynamics through their points of equilibrium and the
stability, obtaining a qualitative classification.
We show numerical simulations, in dimension one, being analyzed and interpreted
biologically. In the spatial simulation, in one dimension, we obtain a wavefront, which
we analyze the speed, the variations of the speed considering some scenarios and the
implications of these changes.
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Efeitos da interação da doxiciclina e adrenomedulina na embolia pulmonar aguda em ovinos anestesiados / Effects of the interaction of doxycycline and adrenomedullin in acute pulmonary embolism in anesthetized sheepRocha, Thalita Leone Alves [UNESP] 29 February 2016 (has links)
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Previous issue date: 2016-02-29 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As metaloproteinases de matriz extracelular (MMPs) podem limitar a vasodilatação pulmonar e os efeitos inotrópicos positivos promovidos pela adrenomedulina durante a hipertensão pulmonar. O presente estudo teve por objetivo avaliar os efeitos da administração combinada da doxiciclina (inibidor não seletivo das MMPs) e da adrenomedulina sobre as alterações hemodinâmicas observadas durante a embolia pulmonar aguda em ovinos. Alterações hemodinâmicas e respiratórias foram mensuradas em ovinos anestesiados, pré-tratados com doxiciclina (10 mg/kg por via intravenosa), submetidos à EPA induzida pela injeção intravenosa (IV) de microesferas de silicone (500 mg) e posteriormente tratados com solução salina (grupo Dox+PE) ou adrenomedulina (50 ng/kg/min) (grupo Dox+PE+Adm). Os resultados deste estudo foram comparados com grupos históricos recentemente publicados por nosso grupo de pesquisa, realizados sob as mesmas condições experimentais, onde foram utilizados ovinos anestesiados não submetidos a qualquer intervenção (grupo Sham) ou submetidos à EPA e tratados com solução salina (grupo PE) ou com adrenomedulina (50 ng/kg/min) (grupo PE+Adm). Doxiciclina não produziu efeitos adicionais sobre as diminuições significativas no índice de resistência vascular pulmonar e aumento no índice cardíaco (ambos em 25%) observadas com o uso da adrenomedulina (grupo PE+Adm). A administração da adrenomedulina (grupo PE+Adm e Dox+PE+Adm) diminuiu significativamente a pressão arterial média e o índice de resistência vascular sistêmica, levando a uma hipotensão sistêmica moderada. Reduções significativas na pressão parcial de oxigênio arterial foram observadas após a doxiciclina e a EPA, que não foram afetadas pela administração da adrenomedulina. Estes resultados demonstram que a administração combinada da doxiciclina e adrenomedulina não traz benefícios hemodinâmicos adicionais quando comparada ao uso isolado da adrenomedulina, sugerindo que está combinação não se apresenta vantajosa durante a EPA induzida por microesferas. / Matrix metalloproteinases (MMPs) may limit severely the pulmonary vasodilatory and inotropic effects of adrenomedullin during pulmonary hypertension. Hemodynamic and respiratory changes were measured in anesthetized bovine pre-treated with doxycycline (10 mg/kg intravenously), subjected to APE induced by intravenous injection of silicone microspheres (500 mg) and subsequently treated with physiological saline (Dox+PE group) or adrenomedullin (50 ng / kg / min) (Dox+PE+ Adm group). The results were compared with historical group recently published by our research group, carried out under the same experimental conditions, where anesthetized sheep were used not subjected to any intervention (Sham group) or subjected to APE, and treated with physiological saline (PE group) or with adrenomedullin (50 ng / kg / min) (PE+Adm Group). Doxycycline produced no effect on significant temporal decreases in pulmonary vascular resistance index and increases in cardiac index (both by 25%) observed with adrenomedullin. The administration of adrenomedullin significantly decreased mean arterial pressure and systemic vascular resistance index, leading to a moderate systemic hypotension. Significant decreases in arterial oxygen partial pressure were observed after doxycycline or APE, but these changes were not affected by adrenomedullin. These results demonstrate that the combined administration of doxycycline and adrenomedullin does not provide additional hemodynamic benefits when compared to isolated use of adrenomedullin, suggesting that this combination does not appear advantageous for the APE-induced microspheres. / FAPESP: 2012/12.291-7
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Chondrocyte Adhesion to RGD-bonded Alginate: Effect on Mechanotransduction and Matrix Metabolism: a DissertationGenes, Nicholas G. 11 August 2003 (has links)
The mechanism of mechanotransduction in chondrocyte matrix metabolism is not well understood, in part because of the density of cartilage and in part because of limitations in in vitroculture systems. Using alginate covalently modified to include the integrin adhesion ligand R-G-D (arginine-glycine-aspartate) represents a unique approach to studying mechanotransduction in that it allows for exploration of the role of integrin adhesion in mediating changes to chondrocyte behavior.
The hypothesis of this research was that chondrocytes will form a cytoskeletal adhesion to RGD-alginate mediated integrins, that this attachment will enable chondrocyte sensation of mechanical signals, and this signaling will alter chondrocyte matrix metabolism. The first aim of this research was to characterize chondrocyte attachment to RGD-alginate, and assess the role of substrate mechanics on chondrocyte attachment kinetics and morphology. Secondly, the effect of chondrocyte attachment to RGD-alginate in 3D culture on matrix biosynthesis was assessed, as were changes in substrate mechanics. Finally, this research aimed to determine the metabolic response of chondrocytes to changes in intrinsic and extrinsic mechanics.
It was found that the RGD ligand functionalized the alginate scaffold, enabling chondrocytes to sense the mechanical environment. Attachment kinetics, morphology, and proteoglycan metabolism were found to adapt to hydrogel matrix stiffness when an integrin adhesion was present. Externally applied compression was transmitted through this integrin attachment, causing changes in proteoglycan synthesis. Components of media serum were found to modulate the effects of integrin mechanotransduction.
These results were obtained by analyzing a novel approach with established techniques, such as the DMB dye assay for sulfated GAG content. The conclusions conform to diverse data from cartilage explant loading and monolayer culture studies, yet were accomplished using one versatile system in a straightforward manner. The potential of this system extends further, into identification of intracellular signaling pathways and extracellular modulation of matrix components. Seeded RGD-alginate is well suited for studying consequences of integrin attachment.
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Mécanismes impliqués dans l'atrophie et la récupération musculaire après immobilisation chez le rat. : Rôle des altérations de la matrice extracellulaire. / Mechanisms involved in muscle atrophy and recovery after immobilization in rats : Role of alterations in the extracellular matrixSlimani, Lamia 26 November 2012 (has links)
Le muscle squelettique est le réservoir principal d’acides aminés libres de l’organisme. Ainsi, l’atrophie musculaire induite par l’immobilisation peut entraîner un affaiblissement et un allongement des périodes de récupération générant des coûts de santé publique élevés. Une aggravation de l’atrophie caractérise de façon surprenante le muscle tibialis anterior (TA) après le déplâtrage, retardant la récupération. Mon objectif a été de comprendre les mécanismes à l’origine de l’aggravation de l’atrophie du TA pendant les phases précoces de récupération en étudiant i) la structure et le phénotype des muscles, ii) la composition de la matrice extracellulaire (MEC), iii) la protéolyse et l’apoptose, et iv) les processus de signalisation via les intégrines. Des rats ont été soumis à une immobilisation par plâtrage pendant 8 jours d’une des deux pattes arrière, l’autre servant de témoin, et placés en récupération pendant 10 jours. L’aggravation de l’atrophie du TA apparaît dès déplâtrage, corrélée avec i) une baisse de l’aire des fibres associée à leur déformation, ii) une redistribution des isoformes des chaines lourdes de myosines, iii) une augmentation de l’apoptose localisée dans le tissu conjonctif, iv) un épaississement de l’endomysium pendant la remobilisation, v) des adaptations au niveau des processus de remodelage des collagènes, et vi) une activation prononcée et persistante du système protéolytique ubiquitine-protéasome (UPS) et de l’apoptosome. Nous montrons également une élévation des niveaux ARNm dans le TA remobilisé vii) de la ténascine-C et de Sparc dès le déplâtrage, et viii) de marqueurs de l’autophagie à partir du moment où l’atrophie se stabilise. Enfin, nous montrons également une élévation des ARNm dans le TA immobilisé ix) des facteurs myogéniques, et x) des intégrines membranaires et de leurs partenaires pendant l’immobilisation et après le déplâtrage. En conclusion, mon travail de thèse a permis de montrer que l'aggravation de l’atrophie du TA est précoce, associée à un remodelage important de la structure et de la composition de la MEC et du phénotype des fibres musculaires, et pourrait résulter de l’augmentation persistante et prononcée de la voie UPS et de l’apoptose. Ce travail suggère que des modifications au niveau des molécules matricielles pendant la remobilisation pourraient influencer la signalisation dépendante des intégrines et la régénération musculaire. / Skeletal muscle is the main reservoir of body amino acids. Thus, muscle atrophy induced by immobilization can lead to a weakening and to a lengthening of recovery periods, leading to elevated healthcare costs. Surprisingly, a worsening of tibialis anterior (TA) muscle atrophy prevailed after cast removal and thus delayed recovery. The aim of my Ph.D was to understand mechanisms underlying the worsening of TA atrophy during early recovery by studying i) the muscle structure and phenotype, ii) the composition of the extracellular matrix (ECM), iii) proteolysis and apoptosis, and iv) the signaling pathways via integrins. Rats were subjected to hindlimb casting for 8 days of one hindllimb, the other leg served as control, and then were allowed to recover for 10 days. The worsening of TA atrophy appeared immediately after cast removal and correlated with i) a decrease in fiber crosssection area associated to fiber deformation, ii) a redistribution of myosin heavy chain isoforms, iii) an increase in apoptosis localized in the connective tissue, iv) a thickening of the endomysium during remobilization, v) some adaptations in collagen remodeling processes, and vi) a pronounced and sustained activation of the ubiquitin-proteasome proteolytic system (UPS) and of the apoptosome. We also showed an increase in the remobilized TA of mRNA levels vii) of tenascin-C and Sparc immediately after cast removal, and viii) of some autophagy markers, when atrophy stabilized. Finally, we showed an elevation of mRNA levels encoding ix) myogenic factors, and x) transmembrane integrins and their partners during TA immobilization and after cast removal. In conclusion, my Ph.D project showed that the worsening of the TA atrophy occurred early after cast removal, was associated with a significant remodeling of the structure and composition of the ECM and of the phenotype of muscle fibers, and may result from pronounced and sustained increase in the UPS and apoptosis. This work suggests that changes in the matricellular matrix molecules during remobilization could influence integrin-dependent signaling and muscle regeneration.
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Ultra-estrutura de células presentes no reparo tecidual sob atividade física moderada /Rodrigues, Rodrigo Ferracine. January 2007 (has links)
Orientador: Flávio Henrique Caetano / Banca: Hércules Menezes / Banca: Ricardo José Gomes / Resumo: Quando um tecido ou órgão é alvo de algum tipo de injúria, dá-se início ao processo de inflamação tecidual. As reações celulares e humorais que tomam parte desta reação são evocadas a fim de exterminar ou neutralizar o agente infeccioso e seus produtos, permitindo que o reparo tecidual se dê da melhor forma possível. Contudo, algumas vezes o resultado desta ação pode ser prejudicial, levando ao comprometimento ou a perda das funções do tecido ou órgão em questão, com conseqüências que podem afetar a saúde do indivíduo como um todo. Em contrapartida, a atividade física moderada tem sido apontada como um grande aliado no combate à várias doenças, potencializando a ação do sistema imune e reduzindo os possíveis danos e minimizando os efeitos nocivos das respostas inflamatórias. Desta forma, nos propomos a verificar os efeitos da atividade física moderada no processo inflamatório e de reparação tecidual, comparando 10 ratos Wistar que realizaram exercícios físicos moderados com 10 sedentários, por meio da análise numérica (microscopia de luz) e ultra-estrutural (microscopia eletrônica de transmissão) de mastócitos, macrófagos e fibroblastos, células muito importantes para tais fenômenos. O modelo de estudo escolhido foi o implante subcutâneo de esponjas de PVC, que mimetiza situações clínicas importantes como, por exemplo, implantes de marcapasso. Nossos resultados indicam que as células do grupo treinado respondem de maneira mais ágil (precoce) e efetiva à injúria, que o número de cada tipo celular foi significativamente maior neste grupo e ainda que, para quaisquer dos grupos, os tipos celulares em estudo agem estreitamente interrelacionados...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: When a tissue or organ is target of some offense, it feels beginning to the process of tissue inflammation. Cellular and humoral reactions that participate of this reaction are evoked to exterminate or to neutralize the infectious agent and your products, allowing the tissue repair to feel in the best possible way. However, the result of this action can sometimes be harmful, taking to the compromising or the loss of the functions of the tissue or organ in subject, with consequences that can affect the individual's health as a completely. On the other hand, the moderate physical activity has been pointed as a great ally in the combat to several diseases, improving the action of the immune system and reducing the possible damages and minimizing the noxious effects of the inflammatory answers. Thus, we intend to verify the effects of the moderate physical activity in the inflammatory and tissue repair process, comparing 10 Wistar rats that had carried through moderate physical exercises with 10 sedentary ones, through the numeric analysis (light microscopy) and ultrastructural (transmission electronic microscopy) of mast cells, macrophages and fibroblasts, which are very important cells for such phenomena. The model of chosen study was the subcutaneous implantation of PVC sponges, that simulates important clinical situations as, for instance, implant of pacemaker. Our results indicate that the cells of the trained group answer in a more agile (precocious) and effective way to the offense, that the number of each cellular type was significantly larger in this group and although, for any of the groups, the cellular types in study act narrowly interrelated. Therefore, we ended in our work that the moderate physical activity can contribute positive and significantly for the inflammation and tissue repair process, making possible that the homeostasis is reestablished more easily and, like this, avoiding larger damages to the individual. / Mestre
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Ultra-estrutura de células presentes no reparo tecidual sob atividade física moderadaRodrigues, Rodrigo Ferracine [UNESP] 20 April 2007 (has links) (PDF)
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rodrigues_rf_me_rcla.pdf: 5396854 bytes, checksum: 53dc5df0dd553ffb8f11bf6074d163cc (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Quando um tecido ou órgão é alvo de algum tipo de injúria, dá-se início ao processo de inflamação tecidual. As reações celulares e humorais que tomam parte desta reação são evocadas a fim de exterminar ou neutralizar o agente infeccioso e seus produtos, permitindo que o reparo tecidual se dê da melhor forma possível. Contudo, algumas vezes o resultado desta ação pode ser prejudicial, levando ao comprometimento ou a perda das funções do tecido ou órgão em questão, com conseqüências que podem afetar a saúde do indivíduo como um todo. Em contrapartida, a atividade física moderada tem sido apontada como um grande aliado no combate à várias doenças, potencializando a ação do sistema imune e reduzindo os possíveis danos e minimizando os efeitos nocivos das respostas inflamatórias. Desta forma, nos propomos a verificar os efeitos da atividade física moderada no processo inflamatório e de reparação tecidual, comparando 10 ratos Wistar que realizaram exercícios físicos moderados com 10 sedentários, por meio da análise numérica (microscopia de luz) e ultra-estrutural (microscopia eletrônica de transmissão) de mastócitos, macrófagos e fibroblastos, células muito importantes para tais fenômenos. O modelo de estudo escolhido foi o implante subcutâneo de esponjas de PVC, que mimetiza situações clínicas importantes como, por exemplo, implantes de marcapasso. Nossos resultados indicam que as células do grupo treinado respondem de maneira mais ágil (precoce) e efetiva à injúria, que o número de cada tipo celular foi significativamente maior neste grupo e ainda que, para quaisquer dos grupos, os tipos celulares em estudo agem estreitamente interrelacionados... / When a tissue or organ is target of some offense, it feels beginning to the process of tissue inflammation. Cellular and humoral reactions that participate of this reaction are evoked to exterminate or to neutralize the infectious agent and your products, allowing the tissue repair to feel in the best possible way. However, the result of this action can sometimes be harmful, taking to the compromising or the loss of the functions of the tissue or organ in subject, with consequences that can affect the individual's health as a completely. On the other hand, the moderate physical activity has been pointed as a great ally in the combat to several diseases, improving the action of the immune system and reducing the possible damages and minimizing the noxious effects of the inflammatory answers. Thus, we intend to verify the effects of the moderate physical activity in the inflammatory and tissue repair process, comparing 10 Wistar rats that had carried through moderate physical exercises with 10 sedentary ones, through the numeric analysis (light microscopy) and ultrastructural (transmission electronic microscopy) of mast cells, macrophages and fibroblasts, which are very important cells for such phenomena. The model of chosen study was the subcutaneous implantation of PVC sponges, that simulates important clinical situations as, for instance, implant of pacemaker. Our results indicate that the cells of the trained group answer in a more agile (precocious) and effective way to the offense, that the number of each cellular type was significantly larger in this group and although, for any of the groups, the cellular types in study act narrowly interrelated. Therefore, we ended in our work that the moderate physical activity can contribute positive and significantly for the inflammation and tissue repair process, making possible that the homeostasis is reestablished more easily and, like this, avoiding larger damages to the individual.
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