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Epithelial cells. --- Cell transformation.

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Epithelial cells. --- Cell transformation.

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"Life on Earth began some 4 billion years ago when the first primitive prokaryotes managed to isolate themselves from the rather hostile environment. The immediate challenge that these first life forms faced was to ensure an optimal balance between two apparently mutually exclusive tasks - protection and separation from the extracellular milieu on the one hand and an efficient exchange of ions, energy sources and metabolites with the very same milieu on the other hand. The commencing evolutionary progress had to address even more challenging problems, such as how to delegate specific cell functions to discrete structures inside of the cell, called organelles (such as the nucleus), and, at the level of multi-cellular organisms, to ensure proper separation of different cell types (e.g. those found in different tissues and organs) while ensuring efficient communication between them. In fact, the human body is highly compartmentalized, from the cell level where local signals are generated and propagated in a highly ordered manner, to the whole body level. This book aims to introduce the interested reader to the universe of these complex segregated compartments in mammals. It discusses how the integrity of different types of barriers - endothelial, epithelial - is normally maintained and what could go wrong when these barriers' permeability becomes abnormally low or high in different disease states. We will focus on several such barriers, which are well studied and which are pivotal for a healthy well-being. In particular, we will focus on the skin, airways, the gut barrier, the endometrium, and cardiovascular and urinary systems. Special reference throughout the book will be made to several most novel groups of potential molecular candidates for the correction of barrier-related dysfunctions, in particular Transient Receptor Potential channels. Hence the title of the book has a triple meaning - a trip in its common sense, TRP channels (as in TRiP database) and Translating Research Into Practice (TRIP). Our team of authors is comprised of physiologists, pharmacologists, biophysicists and medics, including the national representative of Ukraine in the European Crohn's and Colitis organization (ECCO) and a member of the Scientific Committee of the European Association of Urologists. We include clinical cases and discuss molecular and cellular mechanisms underlying such real-life problems in-depth"--

Epithelial cells. --- Diseases. --- Molecular microbiology.

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Epithelial Cells --- Thymus Gland --- Mice, Inbred C3H

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The thyroid is an endocrine gland composed of spheroid epithelial structures, the follicles, which produce the thyroid hormones. The exocrine pancreas secretes and carries the enzymes necessary for digestion through a network of branched epithelial ducts connected to the duodenum. These two organs with different functions and architectures bud from distinct region of the endoderm and first form a mass of epithelial cells. Subsequent reorganization of the epithelial cell mass will give rise either to a multitude of closed and independent epithelial monolayers, the thyroid follicles, or to a single open and branched monolayer in the pancreas. The laboratory aims at understanding the molecular and cellular mechanisms involved in the epithelial mass => monolayer transition and in the choice between spherical or tubular architecture. In the first part of my master thesis, I studied the role of the Camp pathway during the reorganization of the thyroid mass. To this aim, I used an ex vivo culture system of thyroid lobes, which mimics the reorganization of the mass into monolayers, and I manipulated the CAMP pathway in the lobes by adding pharmacological agents known to modulate this pathway. Agents were selected based on changes => monolayer transition by three-dimensional imaging. Finally, phosphorylation of the CREB transcription factor was analyzed in cultured lobes and in thyroid at various developmental stages. The goal of the second part was to collect quantitative biological data for the future development and calibration of a mathematical model to study the epithelial mass => monolayer transition. I focused on three parameters potentially involved in the reorganization: abundance and invasion of endothelial cells cohesion between epithelial cells and adhesion to the extracellular matrix. I first determined the relative abundance of epithelial and endothelial cells in the thyroid and pancreas at the epithelial mass and monolayers stages, using morphometric methods. In parallel, I measured by RT-qPCR the expression of Vegf-a, a factor involved in endothelial cell recruitment and invasion, of cadherins , ensuring cohesion between epithelial cells, and of integrin’s , involved in the adhesion of epithelial cells with the extracellular matrix. La thyroïde est une glande endocrine composée de structures épithéliales sphéroïdes produisant les hormones thyroïdiennes, les follicules.Le pancréas exocrine produit et transporte des enzymes nécessaires à la digestion, grâce à un réseau de canaux épithéliaux branché et connecté au duodénum. Ces deux organes de fonction et d'architecture différentes se développent durant la vie embryonnaire par bourgeonnement de l'endoderme et forment d'abord une structure transitoire semblable : un amas de cellules épithéliales. La réorganisation de cet amas donnera une multitude de monocouches épithéliales fermées et indépendantes dans la thyroïde ou une seule monocouche branchée ouverte dans le pancréas. Le laboratoire étudie les mécanismes moléculaires et cellulaires impliqués dans la réorganisation amas -7 monocouche et dans le choix entre une architecture sphérique ou tubulaire. Au cours de ce travail, j'ai poursuivi une première approche candidat visant à étudier le rôle de la voie AMPc dans la réorganisation de l'amas thyroïdien en follicules. Pour ce faire, j'ai utilisé un système de culture de lobes thyroïdiens, mimant la réorganisation de l'amas en monocouches, et manipulable par ajout d'agents stimulateurs ou inhibiteurs de la voie AMPc. Après m'être assurée que ce système de culture répondait à ces agents en modulant l'expression de gènes cibles de la voie AMPc, j'ai étudié les effets de ces traitements sur la réorganisation amas -7 monocouche, par imagerie en trois dimensions. Finalement, la phosphorylation du facteur de transcription CREB a été analysée dans les lobes en culture et au cours du développement embryonnaire de la thyroïde. Dans une seconde approche, j'ai collecté des données biologiques quantitatives en vue du développement et de la calibration d'un modèle mathématique visant à mieux comprendre la réorganisation amas -7 monocouche. Je me suis focalisée sur trois paramètres potentiellement impliqués dans la réorganisation : l'invasion des cellules endothéliales, la cohésion entre cellules épithéliales et l'adhésion à la matrice extracellulaire. J'ai tout d'abord déterminé l'abondance relative des cellules épithéliales et endothéliales dans la thyroïde et le pancréas aux stades amas et monocouches, en développant des outils de morphométrie. En parallèle, j'ai mesuré par RT-qPCR l'expression du facteur Vegf-a, responsable du recrutement et de l'invasion des cellules endothéliales ainsi que celle des cadhérines assurant la cohésion entre les cellules épithéliales, et des intégrines, impliquées dans l'adhésion des cellules à la matrice extracellulaire .

Epithelial Cells --- Adenosine A3 Receptor Antagonists