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The gut is colonized by bacteria living in symbiosis with the host, forming the gut microbiota. It is considered a therapeutic target since it plays a crucial role in energetic homeostasis, endocrine functions and the immune system and maintains the integrity of the barrier function. Cancer cachexia is a syndrome composed of loss of lean and fat mass, anorexia, insulin resistance and systemic inflammation. There is no curative treatment today, although this syndrome highly reduces the quality of life of patients and is responsible for 20 % of the deaths antibiotic-associated hemorrhagic colitis. K oxytoca has been administrated to mice to determine the impact of this bacterium on cellular proliferation, the morphology and the barrier function of the gut, the immune system, as well as the muscle atrophy observed in cancer cachexia. The administration of K oxytoca does not exacerbate the cancer cachexia since there is no accentuation of the muscle atrophy, nor a significant impact on the immune system of the diseased mice. However, this bacterium could participate in the alteration of the barrier function since the depth of the crypts and the expression of Mki67 are increased in the ileum of the cachectic mice that received K. Oxytoca. Furthermore, there is a significant presence of bacteria in the mesenteric lymph nodes of these mice compared to the lice that did not received the supplementation of bacteria. This suggests that K oxytoca could impact the host’s gut barrier only in the conditions of cancer cachexia, with a high level of this bacterium in the gut. Le microbiote intestinal est composé d’un ensemble de bactéries qui vivent en symbiose avec l’hôte. Un dialogue existe entre le microbiote intestinal et certains organes présents en dehors de l’intestin, raison pour laquelle le microbiote intestinal est un cible thérapeutique intéressante qui pourrait, une fois le profil modifié, contribuer au bon état de santé de l’hôte. Les patients atteints de cachexie cancéreuse présentent un syndrome regroupant les phénomènes de perte de masse maigre et de masse grasse, une résistance à l’insuline, une anorexie et une inflammation systémique. La recherche d’un traitement curatif semble cruciale car les personnes qui en souffrent présentent une qualité de vie fortement diminuée. La cachexie est responsable de 20% des décès des patients cancéreux et il n’existe pas encore de remède à l’heure actuelle. La transposition de la cachexie cancéreuse chez la souris par le modèle C26 a permis de détecter une perturbation de la composition du microbiote intestinal, appelée dysbiose, caractérisée par une augmentation de la présence d’entérobactéries, en particulier Klebsiella oxytoca. Il s’agit d’un pathobiont responsable de colite hémorragique associée à une prise d’antibiotiques et d’infections nosocomiales. K. oxytoca a été administrée à des souris saines et cancéreuses cachectiques afin de déterminer son impact sur la fonction barrière, la prolifération cellulaire et la morphologie de l’intestin, l’atrophie musculaire observée lors de cachexie cancéreuse et le système immunitaire. L’administration de K. oxytoca n’a pas aggravé l’état cachectique des souris cancéreuses étant donné qu’il n’y a pas d’exacerbation de l’atrophie musculaire présente en cas de cachexie cancéreuse, ni d’impact significatif sur le système immunitaire des souris. Cependant, cette bactérie pourrait participer à l’altération de la barrière intestinale via une augmentation significative de l’expression de Mki67, de la profondeur des cryptes intestinales ainsi que la présence de bactéries dans les ganglions mésentériques. K. oxytoca pourrait donc induire des altérations de la barrière intestinale dans des conditions de cachexie cancéreuse avec un taux élevé de cette bactérie au sein du microbiote intestinal. En conclusion, les données obtenues au cours de ce mémoire suggèrent qu’une bactérie augmentée en cas de cachexie, K. oxytoca, contribue aux altérations de l’intestin observée dans ce modèle.

Klebsiella oxytoca --- Gastrointestinal Microbiome --- Cachexia --- Carcinogenicity Tests --- beta-Defensins

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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.

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

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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.

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

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

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.

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 --- 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