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Régulation du facteur de transcription ZONAB dans les cellules épithéliales durant le cycle cellulaire

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ZONAB (Zonula Occludens-1 associated Nucleic Acid Binding) is a transcription factor that stimulates the expression of genes involved in the proliferation of epithelial ceils while repressing that of genes involved in differentiation. Expression of ZONAB is high during embryogenesis, when cells proliferate, and it declines with organ differentiation to eventually disappear in adults. These data indicate an inverse relationship between the amount of ZONAB and differentiation and suggest the existence of mechanisms regulating ZONAB expression as a function of the cellular state. Interestingly, ZONAB is re-expressed in kidney clear cell carcinomas, which are characterized by dedifferentiation and proliferation. In this context, the aim of my work was to study the regulation of ZONAB expression, focusing on its post-translational regulation, as a function of the proliferative and differentiated state. To reach that aim, we cultured a mouse hepatoblast-derived celi une (BMEL) in three different settings: • When BMEL cells are maintained in standard culture condition, here referred as monolayer, they express ZONAB at a constant and high level. • When cells are grown in aggregates, they differentiate into hepatocytes and ZONAB disappears within 24 hours both at the mRNA and protein level. On these aggregates, we tested the implication of the proteasome in the regulation of ZONAB expression by culturing BMEL in the presence of proteasome inhibitors. Although this treatment stabilize ZONAB, as well as its mRNA, and inhibit cell differentiation, inhibition of the proteasome blocked BMEL cell aggregation. • Finally, by serum starvation or addition, we demonstrate that ZONAB expression level can also be modulated. In the absence of serum, the amount of ZONAB mRNA decreases in 24h and the protein disappears in 48h. Surprisingly, differentiation markers are stimulated in 6h of culture. After addition of serum on BMEL that have been starved three days, ZONAB mRNA accumulates progressively while the differentiation markers are lost within 3h. In conclusion, we have found a cellular model (BMEL) in which ZONAB is expressed and where its expression can be modulated (aggregates and serum). Our data suggest that in addition to ZONAB degradation by the proteasome, a transcriptional regulation of ZONAB mRNA also operates. Moreover, the rapidity with which these events occur, when BMEL are cultured in aggregates or in the absence of serum, support the hypothesis of a regulation of ZONAB expression level during the cell cycle. Finally, and unexpectedly, this work demonstrates a decoupling between the expression of ZONAB and cellular differentiation Le facteur de transcription ZONAB (Zonula Occludens-1 associated Nucleic Acid Binding) stimule la transcription de gènes impliqués dans la prolifération tout en réprimant celle de gènes de différenciation. L’expression de ZONAB est élevée durant l’embryogenèse, lorsque les cellules prolifèrent, et elle diminue avec la différenciation des organes pour finalement disparaître chez l’adulte. Ces données révèlent une relation inverse entre la quantité de ZONAB et la différenciation et suggèrent une régulation du niveau d’expression de ZONAB en fonction de l’état cellulaire. De manière intéressante, ZONAB est ré-exprimé dans les carcinomes à cellules claires du rein qui sont caractérisés par une dédifférenciation et un retour à la prolifération. Dans ce contexte, le but de ce travail a été d’étudier la régulation de l’expression de ZONAB, en se focalisant sur sa régulation post-traductionnelle, en fonction de l’état prolifératif et différencié. Pour atteindre ce but, nous avons cultivé une lignée cellulaire dérivée d’hépatoblastes murins (BMEL) dans trois conditions différentes • Dans les conditions de maintien de la culture en monocouche, les BMEL expriment ZONAB à un niveau constant et élevé. • Lorsque les cellules sont cultivées en agrégats, elles se différencient en hépatocytes et ZONAB disparaît endéans 24 heures tant au niveau ARNm que protéique. Sur ces agrégats, nous avons testé l’implication du protéasome dans la régulation de ZONAB en cultivant les BMEL en présence d’inhibiteurs du protéasome. Bien que ce traitement stabilise ZONAB ainsi que son ARNm et inhibe la différenciation des cellules, il empêche également la formation des agrégats. • Enfin, par privation et ajout de sérum, nous montrons que le niveau d’expression de ZONAB peut également être modulé. Sans sérum, la quantité d’ARNm de ZONAB diminue en 24h et la protéine disparaît en 48h. Par contre, les marqueurs de différenciation sont stimulés dès 6h de culture. En ajoutant du sérum aux BMEL qui en ont été privées pendant 3 jours, l’ARNm de ZONAB s’accumule progressivement alors que les marqueurs de différenciation disparaissent en 3h. En conclusion, nous avons trouvé un modèle cellulaire (BMEL) dans lequel ZONAB est exprimé et où son niveau d’expression est modulable (agrégats et sérum). Nos données suggèrent qu’en plus d’un mécanisme de dégradation de ZONAB par le protéasome, il existe une régulation transcriptionnelle de son ARNm. De plus, la rapidité avec laquelle ces effets sont observés, lorsque les BMEL sont cultivées en agrégats ou en absence de sérum, conforte l’hypothèse d’une régulation au cours du cycle cellulaire. Finalement, et de manière inattendue, ce travail démontre un découplage entre l’expression de ZONAB et la différenciation cellulaire


Book
Laboratory guide to the tight junction
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ISBN: 012818647X 9780128226438 0128226439 9780128186473 Year: 2020 Publisher: London : Academic Press,

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Book
Biomedical applications of lanthanum
Authors: --- ---
ISBN: 1617615110 9781617615115 9781617289064 161728906X 9781617289064 Year: 2010 Publisher: New York


Book
Tight Junctions
Authors: ---
ISBN: 9783030972042 Year: 2022 Publisher: Cham Springer International Publishing :Imprint: Springer


Book
The paracellular channel : biology, physiology, and disease
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ISBN: 0128146362 0128146354 9780128146361 9780128146354 Year: 2019 Publisher: London, United Kingdom : Academic Press, an imprint of Elsevier,

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The Paracellular Channel: Biology, Physiology and Disease serves as the first volume to offer a cohesive and unifying picture of the critical functions of paracellular channels (tight junctions) in different tissues. This new class of ion channel utilizes a completely different mechanism to create ion passage pathways across the cell junction. This volume outlines common principles that govern the organization and regulation of these diverse cellular structures, describes the methodology of study, and highlights the pathophysiologic consequence of abnormal structure and functions of the paracellular channels in human diseases. Coverage includes biochemical, biophysical, structural, physiologic analyses of the paracellular channel, and new technologies for recording and characterization.--

Tight junctions
Author:
ISBN: 1280800283 9786610800285 0387366733 0387332014 1441941150 Year: 2006 Publisher: Georgetown, TX : New York, N.Y. : Landes Bioscience/Eurekah.com ; Springer Science+Business Media,

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ight junctions (TJs) are cell-ceil adhesion belts that encircle epithelial and endothelial cells at the limit between the apical and the lateral T-membrane. These junctions are crucial for the establishment of separate compartments in multicellular organisms and for the exchange of substances between the internal milieu and the external environment. The perception of TJs has changed over the years. From being regarded as static paracellular seals, they have come to be perceived as dynamic structures that adjust their morphol­ogy and function in response to physiological, pharmacological and pathologi­cal challenges. The roles that TJs play in epithelial and endothelial cells has also widened, and nowadays this structure is regarded not only as a fence that limits within the membrane, the movement of proteins and lipids between the apical and basolateral membranes, or as a gate that regulates in a size and charge selec­tive manner the transit of ion and molecules through the paracellular pathway, but also as a structure integrated by molecules that participate in the control of cell proliferation. These observations highlight the importance of understand­ing TJ physiology in order to develop effective strategies for the treatment of pathological conditions such as cancer and autoimmune diseases. This broader perception of TJs is reflected in all the chapters of the book and has been attained thanks to the identification in recent years of a wide array of proteins that constitute TJs in epithelial and endothelial cells as well as in central nervous system myelin.


Book
Tight junctions in cancer metastasis
Authors: ---
ISBN: 9400798067 9400760272 9400760280 1299408079 Year: 2013 Publisher: Dordrecht : Springer,

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There has been a dramatic increase in knowledge of tight junctions in the past decade. The molecular structure of tight junctions, cellular functions and the pathophysiological roles of tight junctions are becoming clear. Of the most important functions, the role of the cellular structure in cancer spread and drug delivery are increasingly realised. It is now clear that there are fundamental changes to tight junctions during the process of cancer development. Tight junctions are also critical to the metastatic process of cancer cells. The cellular structure is also crucial in drug therapies, namely, the permeability and bioavailability of the drugs, penetration of barriers such as the blood brain barrier. This current volume aims to summarise the current knowledge of tight junctions, their role in cancer and cancer metastasis and is of interest to scientists and clinicians.


Book
The Tight Junction and Its Proteins : More Than Just a Barrier
Authors: ---
Year: 2020 Publisher: Basel, Switzerland MDPI - Multidisciplinary Digital Publishing Institute

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For a long time, the tight junction (TJ) was known to form and regulate the paracellular barrier between epithelia and endothelial cell sheets. Starting shortly after the discovery of the proteins forming the TJ—mainly the two families of claudins and TAMPs—several other functions have been discovered, a striking one being the surprising finding that some claudins form paracellular channels for small ions and/or water. This Special Issue includes 43 articles covering numerous dedicated topics including pathogens affecting the TJ barrier, TJ regulation via immune cells, the TJ as a therapeutic target, TJ and cell polarity, function and regulation by proteins of the tricellular TJ, TJ as a regulator of cellular processes, organ- and tissue-specific functions, TJ as sensors and reacting to environmental conditions, and last but not least, TJ proteins and cancer.

Keywords

Medicine --- tissue barrier --- tight junction --- claudins --- tricellulin --- tight junctions --- organ preservation --- intestine --- transplantation --- ischemia --- intestinal mucosa --- lung --- epithelia --- interleukin 13 --- UBE2Z --- ubiquitin --- osmolality --- hydrostatic pressure --- cancer --- sensor --- tricellular tight junctions --- endometrial cancer --- epithelial barrier dysfunction --- Claudin-7 --- permeability --- WNK4 --- epithelial sodium channel (ENaC), collecting duct cells --- claudin-1 --- hydrogen peroxide --- phosphorylation --- claudin --- angulin --- drug development --- angubindin-1 --- Clostridium perfringens enterotoxin --- Clostridium perfringens iota-toxin --- antibody --- Mz-ChA-1 cells --- biliary epithelial cells --- phosphatidylcholine --- mucus --- paracellular transport --- atopic dermatitis --- cytokines --- STAT3 --- ZO-2 --- cholestasis --- gene transcription --- hypertrophy --- tumor suppressor --- NLS --- NES --- CaSR --- RhoA --- barrier function --- paracellular permeability --- antidiuretic hormone --- Claudin-14 --- CLDN14 --- hearing loss --- vestibular function --- cochlear implantation --- Hepatitis C Virus --- viral entry --- epidermal barrier --- reconstructed human epidermis --- claudin targeting --- Campylobacter jejuni --- curcumin --- apoptosis --- co-culture --- mouse colon --- TNF --- NFκB --- lipolysis-stimulated lipoprotein receptor (LSR) --- epithelial barrier --- cell–cell contact --- caspase --- kidney stones --- ion reabsorption --- quercetin --- brain barriers --- blood-brain barrier --- neurovascular unit --- blood-cerebrospinal fluid barrier --- arachnoid barrier --- glia limitans --- adherens junctions --- paracellular sodium transport --- thick ascending limb --- nephropathy --- HELIX syndrome --- hypokalemia --- hypermagnesemia --- anhidrosis --- gland dysfunction --- aging --- blood–brain barrier --- mutations --- kidney --- liver --- skin --- human --- mice --- disease --- in silico --- drug discovery --- membrane proteins --- protein interactions --- molecular dynamics --- antibiotic-associated hemorrhagic colitis --- Klebsiella oxytoca --- tight junction assembly --- monocytes --- celiac disease --- claudin-2 --- epithelium --- inflammation --- fibrosis --- proliferation --- migration --- tricellular tight junction --- paracellular water transport --- tight epithelium --- MDCK C7 cells --- cell growth --- endothelia --- adherens junction --- apical junctional complex --- AMP-activated protein kinase (AMPK) --- paracellular barrier --- protein structure --- protein domain --- occludin --- junctional adhesion molecule --- zonula occludens --- MAGUK proteins --- PDZ domain --- stem cell --- chemoresistance --- retinal pigment epithelium --- retinopathy --- barrier formation --- collecting duct --- claudin-5 --- neuropathic pain --- nerve injury --- dorsal root ganglion --- enteropathogenic E. coli (EPEC) --- tight junctions (TJ) --- polarity --- atypical aPKCζ --- transepithelial electrical resistance (TER) --- sorting nexin 9 (SNX9) --- EspF --- claudin 1 --- tumor --- metastasis --- epithelial to mesenchymal transition --- cerebral cavernous malformation --- endothelial barrier --- Rho --- ROCK --- MEKK3 --- ion transport --- ion channel --- super-resolution microscopy --- structured illumination microscopy --- stimulated emission depletion --- single molecule localization microscopy --- Claudin --- blood-biliary barrier --- chronic liver disease --- hepatocellular carcinoma --- cholangiocellular carcinoma --- NISCH syndrome --- repair --- NHE2 --- ClC-2 --- inflammatory bowel disease --- mucosal immunology --- ZO-1 --- actomyosin --- aquaporin --- drinking rate --- epithelial fluid transport --- enterocyte --- osmoregulation --- paracellular --- proximal tubule --- calcium permeability --- claudin-12 --- paracellular channels and barriers --- cell polarity --- pathogens --- immune cells --- environmental sensors


Book
The Tight Junction and Its Proteins: More Than Just a Barrier : More Than Just a Barrier
Authors: ---
Year: 2020 Publisher: Basel, Switzerland MDPI - Multidisciplinary Digital Publishing Institute

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Abstract

For a long time, the tight junction (TJ) was known to form and regulate the paracellular barrier between epithelia and endothelial cell sheets. Starting shortly after the discovery of the proteins forming the TJ—mainly the two families of claudins and TAMPs—several other functions have been discovered, a striking one being the surprising finding that some claudins form paracellular channels for small ions and/or water. This Special Issue includes 43 articles covering numerous dedicated topics including pathogens affecting the TJ barrier, TJ regulation via immune cells, the TJ as a therapeutic target, TJ and cell polarity, function and regulation by proteins of the tricellular TJ, TJ as a regulator of cellular processes, organ- and tissue-specific functions, TJ as sensors and reacting to environmental conditions, and last but not least, TJ proteins and cancer.

Keywords

Medicine --- tissue barrier --- tight junction --- claudins --- tricellulin --- tight junctions --- organ preservation --- intestine --- transplantation --- ischemia --- intestinal mucosa --- lung --- epithelia --- interleukin 13 --- UBE2Z --- ubiquitin --- osmolality --- hydrostatic pressure --- cancer --- sensor --- tricellular tight junctions --- endometrial cancer --- epithelial barrier dysfunction --- Claudin-7 --- permeability --- WNK4 --- epithelial sodium channel (ENaC), collecting duct cells --- claudin-1 --- hydrogen peroxide --- phosphorylation --- claudin --- angulin --- drug development --- angubindin-1 --- Clostridium perfringens enterotoxin --- Clostridium perfringens iota-toxin --- antibody --- Mz-ChA-1 cells --- biliary epithelial cells --- phosphatidylcholine --- mucus --- paracellular transport --- atopic dermatitis --- cytokines --- STAT3 --- ZO-2 --- cholestasis --- gene transcription --- hypertrophy --- tumor suppressor --- NLS --- NES --- CaSR --- RhoA --- barrier function --- paracellular permeability --- antidiuretic hormone --- Claudin-14 --- CLDN14 --- hearing loss --- vestibular function --- cochlear implantation --- Hepatitis C Virus --- viral entry --- epidermal barrier --- reconstructed human epidermis --- claudin targeting --- Campylobacter jejuni --- curcumin --- apoptosis --- co-culture --- mouse colon --- TNF --- NFκB --- lipolysis-stimulated lipoprotein receptor (LSR) --- epithelial barrier --- cell–cell contact --- caspase --- kidney stones --- ion reabsorption --- quercetin --- brain barriers --- blood-brain barrier --- neurovascular unit --- blood-cerebrospinal fluid barrier --- arachnoid barrier --- glia limitans --- adherens junctions --- paracellular sodium transport --- thick ascending limb --- nephropathy --- HELIX syndrome --- hypokalemia --- hypermagnesemia --- anhidrosis --- gland dysfunction --- aging --- blood–brain barrier --- mutations --- kidney --- liver --- skin --- human --- mice --- disease --- in silico --- drug discovery --- membrane proteins --- protein interactions --- molecular dynamics --- antibiotic-associated hemorrhagic colitis --- Klebsiella oxytoca --- tight junction assembly --- monocytes --- celiac disease --- claudin-2 --- epithelium --- inflammation --- fibrosis --- proliferation --- migration --- tricellular tight junction --- paracellular water transport --- tight epithelium --- MDCK C7 cells --- cell growth --- endothelia --- adherens junction --- apical junctional complex --- AMP-activated protein kinase (AMPK) --- paracellular barrier --- protein structure --- protein domain --- occludin --- junctional adhesion molecule --- zonula occludens --- MAGUK proteins --- PDZ domain --- stem cell --- chemoresistance --- retinal pigment epithelium --- retinopathy --- barrier formation --- collecting duct --- claudin-5 --- neuropathic pain --- nerve injury --- dorsal root ganglion --- enteropathogenic E. coli (EPEC) --- tight junctions (TJ) --- polarity --- atypical aPKCζ --- transepithelial electrical resistance (TER) --- sorting nexin 9 (SNX9) --- EspF --- claudin 1 --- tumor --- metastasis --- epithelial to mesenchymal transition --- cerebral cavernous malformation --- endothelial barrier --- Rho --- ROCK --- MEKK3 --- ion transport --- ion channel --- super-resolution microscopy --- structured illumination microscopy --- stimulated emission depletion --- single molecule localization microscopy --- Claudin --- blood-biliary barrier --- chronic liver disease --- hepatocellular carcinoma --- cholangiocellular carcinoma --- NISCH syndrome --- repair --- NHE2 --- ClC-2 --- inflammatory bowel disease --- mucosal immunology --- ZO-1 --- actomyosin --- aquaporin --- drinking rate --- epithelial fluid transport --- enterocyte --- osmoregulation --- paracellular --- proximal tubule --- calcium permeability --- claudin-12 --- paracellular channels and barriers --- cell polarity --- pathogens --- immune cells --- environmental sensors


Book
The Tight Junction and Its Proteins: More Than Just a Barrier : More Than Just a Barrier
Authors: ---
Year: 2020 Publisher: Basel, Switzerland MDPI - Multidisciplinary Digital Publishing Institute

Loading...
Export citation

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Bookmark

Abstract

For a long time, the tight junction (TJ) was known to form and regulate the paracellular barrier between epithelia and endothelial cell sheets. Starting shortly after the discovery of the proteins forming the TJ—mainly the two families of claudins and TAMPs—several other functions have been discovered, a striking one being the surprising finding that some claudins form paracellular channels for small ions and/or water. This Special Issue includes 43 articles covering numerous dedicated topics including pathogens affecting the TJ barrier, TJ regulation via immune cells, the TJ as a therapeutic target, TJ and cell polarity, function and regulation by proteins of the tricellular TJ, TJ as a regulator of cellular processes, organ- and tissue-specific functions, TJ as sensors and reacting to environmental conditions, and last but not least, TJ proteins and cancer.

Keywords

tissue barrier --- tight junction --- claudins --- tricellulin --- tight junctions --- organ preservation --- intestine --- transplantation --- ischemia --- intestinal mucosa --- lung --- epithelia --- interleukin 13 --- UBE2Z --- ubiquitin --- osmolality --- hydrostatic pressure --- cancer --- sensor --- tricellular tight junctions --- endometrial cancer --- epithelial barrier dysfunction --- Claudin-7 --- permeability --- WNK4 --- epithelial sodium channel (ENaC), collecting duct cells --- claudin-1 --- hydrogen peroxide --- phosphorylation --- claudin --- angulin --- drug development --- angubindin-1 --- Clostridium perfringens enterotoxin --- Clostridium perfringens iota-toxin --- antibody --- Mz-ChA-1 cells --- biliary epithelial cells --- phosphatidylcholine --- mucus --- paracellular transport --- atopic dermatitis --- cytokines --- STAT3 --- ZO-2 --- cholestasis --- gene transcription --- hypertrophy --- tumor suppressor --- NLS --- NES --- CaSR --- RhoA --- barrier function --- paracellular permeability --- antidiuretic hormone --- Claudin-14 --- CLDN14 --- hearing loss --- vestibular function --- cochlear implantation --- Hepatitis C Virus --- viral entry --- epidermal barrier --- reconstructed human epidermis --- claudin targeting --- Campylobacter jejuni --- curcumin --- apoptosis --- co-culture --- mouse colon --- TNF --- NFκB --- lipolysis-stimulated lipoprotein receptor (LSR) --- epithelial barrier --- cell–cell contact --- caspase --- kidney stones --- ion reabsorption --- quercetin --- brain barriers --- blood-brain barrier --- neurovascular unit --- blood-cerebrospinal fluid barrier --- arachnoid barrier --- glia limitans --- adherens junctions --- paracellular sodium transport --- thick ascending limb --- nephropathy --- HELIX syndrome --- hypokalemia --- hypermagnesemia --- anhidrosis --- gland dysfunction --- aging --- blood–brain barrier --- mutations --- kidney --- liver --- skin --- human --- mice --- disease --- in silico --- drug discovery --- membrane proteins --- protein interactions --- molecular dynamics --- antibiotic-associated hemorrhagic colitis --- Klebsiella oxytoca --- tight junction assembly --- monocytes --- celiac disease --- claudin-2 --- epithelium --- inflammation --- fibrosis --- proliferation --- migration --- tricellular tight junction --- paracellular water transport --- tight epithelium --- MDCK C7 cells --- cell growth --- endothelia --- adherens junction --- apical junctional complex --- AMP-activated protein kinase (AMPK) --- paracellular barrier --- protein structure --- protein domain --- occludin --- junctional adhesion molecule --- zonula occludens --- MAGUK proteins --- PDZ domain --- stem cell --- chemoresistance --- retinal pigment epithelium --- retinopathy --- barrier formation --- collecting duct --- claudin-5 --- neuropathic pain --- nerve injury --- dorsal root ganglion --- enteropathogenic E. coli (EPEC) --- tight junctions (TJ) --- polarity --- atypical aPKCζ --- transepithelial electrical resistance (TER) --- sorting nexin 9 (SNX9) --- EspF --- claudin 1 --- tumor --- metastasis --- epithelial to mesenchymal transition --- cerebral cavernous malformation --- endothelial barrier --- Rho --- ROCK --- MEKK3 --- ion transport --- ion channel --- super-resolution microscopy --- structured illumination microscopy --- stimulated emission depletion --- single molecule localization microscopy --- Claudin --- blood-biliary barrier --- chronic liver disease --- hepatocellular carcinoma --- cholangiocellular carcinoma --- NISCH syndrome --- repair --- NHE2 --- ClC-2 --- inflammatory bowel disease --- mucosal immunology --- ZO-1 --- actomyosin --- aquaporin --- drinking rate --- epithelial fluid transport --- enterocyte --- osmoregulation --- paracellular --- proximal tubule --- calcium permeability --- claudin-12 --- paracellular channels and barriers --- cell polarity --- pathogens --- immune cells --- environmental sensors

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