Claudins: A large family of transmembrane proteins found in TIGHT JUNCTIONS. They take part in the formation of paracellular barriers and pores that regulate paracellular permeability.Claudin-3: A ubiquitously-expressed claudin subtype that acts as a general barrier-forming protein in TIGHT JUNCTIONS. Elevated expression of claudin-3 is found in a variety of tumor cell types, suggesting its role as a therapeutic target for specific ANTINEOPLASTIC AGENTS.Claudin-4: A claudin subtype that takes part in maintaining the barrier-forming property of TIGHT JUNCTIONS. Claudin-4 is found associated with CLAUDIN-8 in the KIDNEY COLLECTING DUCT where it may play a role in paracellular chloride ion reabsorption.Tight Junctions: Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. (Alberts et al., Molecular Biology of the Cell, 2nd ed, p22)Claudin-1: An integral membrane protein that is localized to TIGHT JUNCTIONS, where it plays a role in controlling the paracellular permeability of polarized cells. Mutations in the gene for claudin-1 are associated with Neonatal Ichthyosis-Sclerosing Cholangitis (NISCH) Syndrome.Occludin: A MARVEL domain protein that plays an important role in the formation and regulation of the TIGHT JUNCTION paracellular permeability barrier.Claudin-5: A claudin subtype that is found localized to TIGHT JUNCTIONS in VASCULAR ENDOTHELIAL CELLS. The protein was initially identified as one of several proteins which are deleted in VELOCARDIOFACIAL SYNDROME and may play an important role in maintaining the integrity of the BLOOD-BRAIN BARRIER.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Zonula Occludens-2 Protein: A zonula occludens protein subtype found in epithelial cell junctions. Several isoforms of zonula occludens-2 protein exist due to use of alternative promoter regions and alternative mRNA splicings.Claudin-2: A claudin subtype that is associated with the formation of cation-selective channels and increased epithelial permeability. It is localized to the TIGHT JUNCTIONS of the PROXIMAL KIDNEY TUBULE and INTESTINAL EPITHELIUM.MARVEL Domain Containing 2 Protein: A tight junction-associated MARVEL protein that may play a role in separating the endolymphatic and perilymphatic spaces of the ORGAN OF CORTI. Defects in the gene that codes for MARVELD2 protein are a cause of deafness autosomal recessive type 49.Zonula Occludens-1 Protein: A 195-kDa zonula occludens protein that is distinguished by the presence of a ZU5 domain at the C-terminal of the molecule.Zonula Occludens Proteins: A family of proteins that play a role in TIGHT JUNCTION formation by binding to and anchoring proteins to the ACTIN CYTOSKELETON.Clostridium perfringens: The most common etiologic agent of GAS GANGRENE. It is differentiable into several distinct types based on the distribution of twelve different toxins.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Tight Junction Proteins: Proteins that take part in the formation or structure of TIGHT JUNCTIONS.Nephrons: The functional units of the kidney, consisting of the glomerulus and the attached tubule.Loop of Henle: The U-shaped portion of the renal tubule in the KIDNEY MEDULLA, consisting of a descending limb and an ascending limb. It is situated between the PROXIMAL KIDNEY TUBULE and the DISTAL KIDNEY TUBULE.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Madin Darby Canine Kidney Cells: An epithelial cell line derived from a kidney of a normal adult female dog.Electric Impedance: The resistance to the flow of either alternating or direct electrical current.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Junctional Adhesion Molecules: A family of membrane glycoproteins localized to TIGHT JUNCTIONS that contain two extracellular Ig-like domains, a single transmembrane segment, and a cytoplasmic tail of variable length.Keratosis, Actinic: White or pink lesions on the arms, hands, face, or scalp that arise from sun-induced DNA DAMAGE to KERATINOCYTES in exposed areas. They are considered precursor lesions to superficial SQUAMOUS CELL CARCINOMA.Freeze Fracturing: Preparation for electron microscopy of minute replicas of exposed surfaces of the cell which have been ruptured in the frozen state. The specimen is frozen, then cleaved under high vacuum at the same temperature. The exposed surface is shadowed with carbon and platinum and coated with carbon to obtain a carbon replica.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Hyperammonemia: Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.Stem Cell Factor: A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.Hematopoietic Cell Growth Factors: These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Mineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)Receptors, Mineralocorticoid: Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.Aldosterone: A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.Sulfacetamide: An anti-infective agent that is used topically to treat skin infections and orally for urinary tract infections.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Coat Protein Complex I: A protein complex comprised of COATOMER PROTEIN and ADP RIBOSYLATION FACTOR 1. It is involved in transport of vesicles between the ENDOPLASMIC RETICULUM and the GOLGI APPARATUS.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.COP-Coated Vesicles: TRANSPORT VESICLES formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of COP (coat protein complex) proteins, either COPI or COPII. COPI coated vesicles transport backwards from the cisternae of the GOLGI APPARATUS to the rough endoplasmic reticulum (ENDOPLASMIC RETICULUM, ROUGH), while COPII coated vesicles transport forward from the rough endoplasmic reticulum to the Golgi apparatus.ADP-Ribosylation Factors: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47ADP-Ribosylation Factor 1: ADP-RIBOSYLATION FACTOR 1 is involved in regulating intracellular transport by modulating the interaction of coat proteins with organelle membranes in the early secretory pathway. It is a component of COAT PROTEIN COMPLEX I. This enzyme was formerly listed as EC 3.6.1.47.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. (1/444)

Members of the newly identified claudin gene family constitute tight junction (TJ) strands, which play a pivotal role in compartmentalization in multicellular organisms. We identified oligodendrocyte-specific protein (OSP) as claudin-11, a new claudin family member, due to its sequence similarity to claudins as well as its ability to form TJ strands in transfected fibroblasts. Claudin-11/OSP mRNA was expressed in the brain and testis. Immunofluorescence microscopy with anti-claudin-11/OSP polyclonal antibody (pAb) and anti-neurofilament mAb revealed that in the brain claudin-11/OSP-positive linear structures run in a gentle spiral around neurofilament-positive axons. At the electron microscopic level, these linear structures were identified as the so-called interlamellar strands in myelin sheaths of oligodendrocytes. In testis, well-developed TJ strands of Sertoli cells were specifically labeled with anti-claudin-11/OSP pAb both at immunofluorescence and electron microscopic levels. These findings indicated that the interlamellar strands of oligodendrocyte myelin sheaths can be regarded as a variant of TJ strands found in many other epithelial cells, and that these strands share a specific claudin species, claudin-11/OSP, with those in Sertoli cells to create and maintain the repeated compartments around axons by oligodendrocytes.  (+info)

Transmembrane proteins in the tight junction barrier. (2/444)

Three types of transmembrane proteins have been identified within the tight junction, but it remains to be determined how they provide the molecular basis for regulating the paracellular permeability for water, solutes, and immune cells. Several of these proteins localize specifically within the continuous cell-to-cell contacts of the tight junction. One of these, occludin, is a cell adhesion molecule that has been demonstrated to influence ion and solute permeability. The claudins are a family of four-membrane spanning proteins; unexpectedly, other members of this family have already been characterized without recognizing their relationship to tight junctions. Junction adhesion molecule, the most recently identified tight junction component, is a member of the Ig superfamily and influences the paracellular transmigration of immune cells. A plaque of cytoplasmic proteins under the junction may be responsible for scaffolding the transmembrane proteins, creating a link to the perijunctional actin cytoskeleton and transducing regulatory signals that control the paracellular barrier.  (+info)

Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. (3/444)

Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.  (+info)

Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions. (4/444)

In multicellular organisms, various compositionally distinct fluid compartments are established by epithelial and endothelial cellular sheets. For these cells to function as barriers, tight junctions (TJs) are considered to create a primary barrier for the diffusion of solutes through the paracellular pathway [1] [2] [3]. In ultrathin sections viewed under electron microscopy, TJs appear as a series of apparent fusions, involving the outer leaflets of plasma membranes of adjacent cells, to form the so-called kissing points of TJs, where the intercellular space is completely obliterated [4]. Claudins are a family of 16 proteins whose members have been identified as major integral membrane proteins localized exclusively at TJs [5] [6] [7] [8]. It remains unclear, however, whether claudins have the cell-adhesion activity that would explain the unusual intercellular adhesion at TJs. Using mouse L-fibroblast transfectants expressing various amounts of claudin-1, -2 or -3, we found that these claudins possess Ca(2+)-independent cell-adhesion activity. Using ultrathin-section electron microscopy, we observed many kissing points of TJs between adjacent transfectants. Furthermore, the cell-adhesion activity of occludin, another integral membrane protein localized at TJs [9] [10] [11], was negligible when compared with that of claudins. Thus, claudins are responsible for TJ-specific obliteration of the intercellular space.  (+info)

Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. (5/444)

Tight junctions (TJs) in endothelial cells are thought to determine vascular permeability. Recently, claudin-1 to -15 were identified as major components of TJ strands. Among these, claudin-5 (also called transmembrane protein deleted in velo-cardio-facial syndrome [TMVCF]) was expressed ubiquitously, even in organs lacking epithelial tissues, suggesting the possible involvement of this claudin species in endothelial TJs. We then obtained a claudin-6-specific polyclonal antibody and a polyclonal antibody that recognized both claudin-5/TMVCF and claudin-6. In the brain and lung, immunofluorescence microscopy with these polyclonal antibodies showed that claudin-5/TMVCF was exclusively concentrated at cell-cell borders of endothelial cells of all segments of blood vessels, but not at those of epithelial cells. Immunoreplica electron microscopy revealed that claudin-5/TMVCF was a component of TJ strands. In contrast, in the kidney, the claudin-5/TMVCF signal was restricted to endothelial cells of arteries, but was undetectable in those of veins and capillaries. In addition, in all other tissues we examined, claudin-5/TMVCF was specifically detected in endothelial cells of some segments of blood vessels, but not in epithelial cells. Furthermore, when claudin-5/TMVCF cDNA was introduced into mouse L fibroblasts, TJ strands were reconstituted that resembled those in endothelial cells in vivo, i.e., the extracellular face-associated TJs. These findings indicated that claudin-5/TMVCF is an endothelial cell-specific component of TJ strands.  (+info)

Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier. (6/444)

Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.  (+info)

Manner of interaction of heterogeneous claudin species within and between tight junction strands. (7/444)

In tight junctions (TJs), TJ strands are associated laterally with those of adjacent cells to form paired strands to eliminate the extracellular space. Claudin-1 and -2, integral membrane proteins of TJs, reconstitute paired TJ strands when transfected into L fibroblasts. Claudins comprise a multigene family and more than two distinct claudins are coexpressed in single cells, raising the questions of whether heterogeneous claudins form heteromeric TJ strands and whether claudins interact between each of the paired strands in a heterophilic manner. To answer these questions, we cotransfected two of claudin-1, -2, and -3 into L cells, and detected their coconcentration at cell-cell borders as elaborate networks. Immunoreplica EM confirmed that distinct claudins were coincorporated into individual TJ strands. Next, two L transfectants singly expressing claudin-1, -2, or -3 were cocultured and we found that claudin-3 strands laterally associated with claudin-1 and -2 strands to form paired strands, whereas claudin-1 strands did not interact with claudin-2 strands. We concluded that distinct species of claudins can interact within and between TJ strands, except in some combinations. This mode of assembly of claudins could increase the diversity of the structure and functions of TJ strands.  (+info)

Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. (8/444)

ZO-1, ZO-2, and ZO-3, which contain three PDZ domains (PDZ1 to -3), are concentrated at tight junctions (TJs) in epithelial cells. TJ strands are mainly composed of two distinct types of four-transmembrane proteins, occludin, and claudins, between which occludin was reported to directly bind to ZO-1/ZO-2/ZO-3. However, in occludin-deficient intestinal epithelial cells, ZO-1/ZO-2/ZO-3 were still recruited to TJs. We then examined the possible interactions between ZO-1/ZO-2/ZO-3 and claudins. ZO-1, ZO-2, and ZO-3 bound to the COOH-terminal YV sequence of claudin-1 to -8 through their PDZ1 domains in vitro. Then, claudin-1 or -2 was transfected into L fibroblasts, which express ZO-1 but not ZO-2 or ZO-3. Claudin-1 and -2 were concentrated at cell-cell borders in an elaborate network pattern, to which endogenous ZO-1 was recruited. When ZO-2 or ZO-3 were further transfected, both were recruited to the claudin-based networks together with endogenous ZO-1. Detailed analyses showed that ZO-2 and ZO-3 are recruited to the claudin-based networks through PDZ2 (ZO-2 or ZO-3)/PDZ2 (endogenous ZO-1) and PDZ1 (ZO-2 or ZO-3)/COOH-terminal YV (claudins) interactions. In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed.  (+info)

We hypothesize that epigenetic control of gene expression in addition to genomic amplifications, deletions and mutations between basal-like and claudin-low breast cancer is a major contributor for enrichment of the claudin-low characteristics in tumors that develop resistance to therapy. We will use two models to test our hypothesis. In vivo the C3Tag GEMM phenotypically resembles triple-negative human breast cancers by gene expression profiles, and shares genetic similarities including the acquisition of KRAS gene amplification and overexpression during tumor development. C3Tag tumors treated with inhibitors of MEK, downstream of KRAS signaling, ultimately progress through therapy. Progression was accompanied by reprogramming of tumors to signal through alternative pathways, with a transformation from "basal-like" to "claudin-low". The in vitro model is SUM229 human breast cancer cells that maintain equilibrium between two populations: one basal-like with enhanced expression of epithelial ...
Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring
IntroductionThe recently identified claudin-low subtype of breast cancer is enriched for cells with stem-like and mesenchymal-like characteristics....
Background: The anti-programmed cell death 1 (PD-1) antibody pembrolizumab is clinically active against non-small cell lung cancer (NSCLC). In addition to T-cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of advanced NSCLC patients, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC. Methods: In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% were randomly allocated to group A (55 patients, pembrolizumab plus NK cells) and group B (54 patients, pembrolizumab alone). The patients received intravenous pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received two cycles of NK cell therapy as one course of treatment. Results: In our study, Group A patients had ...
Objective(s) The growing trend of research demonstrates that dynamic expression of two metastasis repressor classes (metastasis suppressor genes and anti-metastatic miRNA) has a close relationship with tumor invasion and metastasis. Using different strategies, it was revealed that cellular levels of miR-31 and Breast cancer Metastasis Suppressor1 (BRMS1) protein, which are among the most significant modulators of metastasis, have a correlation with the cells capability for invading and metastasizing; cells containing higher levels of miR-31 or BRMS1 were less metastatic. This project was carried out to determine whether the combinations of miR-31 and BRMS1 genes are able to enhance the capability of repressing the claudin-low breast cancer cell (MDA-MB-231) invasion. Materials and Methods This study used a restoration-based approach by miR-31 mimic and optimized BRMS1 gene sequences, which were cloned into a chimeric construct and transfected to the MDA-M231cells. Results Our data revealed that the
Claudins are a family of proteins that are the most important components of the tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm. Claudins are small (20-27 kilodalton (kDa)) transmembrane proteins which are found in many organisms, ranging from nematodes to human beings, and are very similar in their structure, although this conservation is not observed on the genetic level. Claudins span the cellular membrane 4 times, with the N-terminal end and the C-terminal end both located in the cytoplasm, and two extracellular loops which show the highest degree of conservation. The first extracellular loop consists on average of 53 amino acids and the second one, being slightly smaller, of 24 amino acids. The N-terminal end is usually very short (4-10 amino acids), the C-terminal end varies in length ...
GGRNA , 2020-04-07 23:23:15 , RefSeq release 60 (20130726)] RefSeq ID Version Symbol GeneID Definition NM_001101389 NM_001101389.1 CLDN25 644672 Homo sapiens claudin 25 (CLDN25), mRNA. NM_001111319 NM_001111319.1 CLDN22 53842 Homo sapiens claudin 22 (CLDN22), mRNA. NM_020982 NM_020982.3 CLDN9 9080 Homo sapiens claudin 9 (CLDN9), mRNA. NM_001001346 NM_001001346.3 CLDN20 49861 Homo sapiens claudin 20 (CLDN20), mRNA. NM_001306 NM_001306.3 CLDN3 1365 Homo sapiens claudin 3 (CLDN3), mRNA. NM_012131 NM_012131.2 CLDN17 26285 Homo sapiens claudin 17 (CLDN17), mRNA. NM_016369 NM_016369.3 CLDN18 51208 Homo sapiens claudin 18 (CLDN18), transcript variant 1, mRNA. NM_001185056 NM_001185056.1 CLDN11 5010 Homo sapiens claudin 11 (CLDN11), transcript variant 2, mRNA. NM_005602 NM_005602.5 CLDN11 5010 Homo sapiens claudin 11 (CLDN11), transcript variant 1, mRNA. NM_182848 NM_182848.3 CLDN10 9071 Homo sapiens claudin 10 (CLDN10), transcript variant a, mRNA. NM_006984 NM_006984.4 CLDN10 9071 Homo sapiens claudin ...
Findings: hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture ...
Sigma-Aldrich offers abstracts and full-text articles by [S K Tiwari-Woodruff, A G Buznikov, T Q Vu, P E Micevych, K Chen, H I Kornblum, J M Bronstein].
View mouse Cldn15 Chr5:136966616-136975858 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Reaktivität: Huhn, Rind (Kuh), Hund and more. 60 verschiedene CLDN18 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The tight junctions (TJ), which are located in the apical region between epithelial and endothelial cells, regulate the paracellular diffusion of ions and small molecules and play an important role in maintaining cell polarity, cell-cell integrity, and permeability. In the lung, epithelial cells are attached by TJ structures. They provide a permeable barrier and cell communication. The loss of barrier integrity, which is maintained by the expression of claudins (Cldn), results in cellular permibilization and leads to paracellular diffusion of solutes and harmful molecules. There are 27 known Cldn homologous members in mice and human. Cldn6 is mostly expressed in embryonic stem cells and associated with the programing of epithelial cells during embryo development and lung morphogenesis. In order to test the hypothesis that Cldn6 expression affects lung morphogenesis, we analyzed the expression pattern of Cldn6 during lung ontogenesis to examine cell-specific expression pattern of Cldn6 during each
Epithelial and endothelial cells form the external lining of outer and inner body surfaces and blood vessels of multicellular organisms. Thus, they create separate compartments each exhibiting an environment optimally adjusted to their respective function. To build up such compartments epithelial and endothelial cells have to restrict the paracellular diffusion of substances. The paracellular cleft is sealed by tight junctions (TJ). In electron microscopical images TJs appear as a network of intermembranous strands in the apical region of the lateral cell membrane of epithelial and endothelial cells. Claudins (Cld) form the structural backbone of TJs. The present study provided evidence for the first time that single amino acids of the second extracellular loop (ECL) of a claudin are essential for the paracellular tightness of epithelial cells. The effect of single amino acid substitutions of the second ECL of Cld5 were studied in cells expressing various other endogenous claudins except Cld5. ...
This gene encodes an integral membrane protein, which belongs to the claudin family. The protein is a component of tight junction strands and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems ...
For every experimental group, brains from at minimum 3 distinct litter had been analyzed and when compared to the in accordance NaCl handle group. qPCR approach improvement exposed that only samples must be when compared to every other which have gone through experimental treatment, mind isolation, storage, purification and evaluation preparing steps with each other. Therefore, for every DEX-treatment the according NaCl handle group was carried out at the exact same time. In addition, owing to the large complete variety of samples, but limited sample variety which could be purified at the same time, only samples from mice at the same age and identical variety of antenatal injections ended up compared to every other by using a two-tailed Student`s t-take a look at. Data are offered as the signifies ± SEM. The major tight junction molecule and mind endothelial mobile marker claudin-five was investigated originally. Triple maternal DEX remedy drastically decreased claudin-5 mRNA expression to .54 ...
The C\terminal fragment of enterotoxin (C\CPE) modulates the tight junction protein claudin and disturbs the tight junctional barrier. epithelial cells (HPDEs) had been treated with C\CPE 194 and C\CPE meters19. In well\differentiated cells of the pancreatic malignancy cell collection HPAC, C\CPE 194 and C\CPE meters19 interrupted both the hurdle and fencing features without adjustments in manifestation of claudin\1 and \4, collectively with an boost of MAPK phosphorylation. C\CPE 194, but not really C\CPE meters19, improved the cytotoxicity of the anticancer brokers gemcitabine and H\1. In differentiated pancreatic malignancy cell collection PANC\1 badly, C\CPE 194, but not really C\CPE meters19, reduced claudin\4 phrase and improved MAPK activity and the cytotoxicity of the anticancer agencies. In regular HPDEs, C\CPE 194 and C\CPE meters19 reduced claudin\4 phrase and improved the MAPK activity, whereas they do not really influence the cytotoxicity of the anticancer agencies. Our results ...
Complete information for CLDN18 gene (Protein Coding), Claudin 18, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Tight junctions between epithelial and endothelial cells form selective barriers and paracellular channels and regulate paracellular transport of solutes, immune cells, and drugs. More specifically, tight junctions consist of proteins that laterally interconnect neighboring cells of epithelia and endothelia. Certain proteins seal the tight junction, so that a nearly impermeable barrier develops, whereas others form channels that allow for permeation between the cells. Recent investigations have focused on tight junction proteins, belonging to the claudin family (claudins-1 to -27 in humans) and the newly defined group of TAMP (three proteins: occludin, Marvel-D2, and tricellulin). Barriers and Channels Formed by Tight Junction Proteins I showcases work in this area clustered around three major themes: the molecular properties of tight junctions, for example, the role of the claudin family of proteins and the formation of ion and charge-selective channels; the regulation of tight junction
From NCBI Gene:. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in ...
immune Uncategorized PA-824, Rabbit Polyclonal to C-RAF (phospho-Thr269). The blood-epididymis barrier (BEB) is formed by epithelial tight junctions mediating selective permeability from the PA-824 epididymal epithelium. the paracellular permeability had been examined by two strategies TER and FITC-Dextran-based tracer diffusion assays. Both assays soon add up to related outcomes indicating a time-dependent disruption from the BEB differentially for the three TGF? isoforms (TGF?3>TGF?1>TGF?2) inside a TGF?-recetor-1 kinase- and Smad-dependent way. The small junction proteins claudin-1 was discovered to be decreased by the procedure with TGF?s whereas occludin had not PA-824 been affected. Epididymal epithelial cells are mainly attentive to TGF?s PA-824 through the basolateral side recommending that TGF? may impact for the epididymal epithelium through the stroma cell tradition versions the knockdown of 1 of the claudins (1 -3 -4 or -7) led to dramatically reduced transepithelial electrical level ...
0011]The tight junctions form a selective barrier regulating the passage of ions and molecules through paracellular space. Under electron microscopy, it is noted that the tight junctions form a series of fusion points between the outer leaflets of the plasma membranes of two adjacent cells. These membrane contact zones appear, by freeze fracture, in the form of a continuous network that surrounds the apex of each cell. This network is constituted by membrane protein polymers, the claudins and occludin which are themselves connected to cytoplasmic proteins among which in particular the zonula occludens proteins (ZO-1 to 3) are to be found. Occludin, the claudins as well as the ZO-1s are often the target for bacterial toxins, leading to an alteration in the organisation and the function of the tight junctions (Coraux et al., Am J Respir Cell Mol Biol 2004, 5:605-612 ...
Background: Metaplastic breast cancer (BC) is a treatment-refractory rare type of BC with characteristics similar to claudin-low tumors. Understanding the genomic landscape of metaplastic BC can lead to identification of new therapies.. Methods: Patients with metastatic metaplastic BC referred for experimental therapies, who had adequate archival tumor tissue for DNA extraction, had targeted next-generation sequencing (NGS) for 3,769 exons of 236 cancer-related genes and 47 introns from 19 genes to an average depth of 1000X using the Illumina HiSeq 2000 platform (Foundation One, Foundation Medicine, MA).. Results: NGS results were obtained for 10 women with metaplastic BC (median age 60 years [39-73], median prior therapies for metastatic BC 0 [0-1]). NGS revealed a total of 41 aberrations in 25 genes and all 10 patients had at least 1 molecular aberration (range 1-7, median 4). Of 41 detected molecular aberrations, 17 (41%) included putative activation of the PI3K/mTOR and/or MAPK pathways ...
Claudin 7 antibody Rabbit Polyclonal from Proteintech validated in Western Blot (WB), Immunohistochemistry (IHC), Immunofluorescence (IF), Enzyme-linked Immunosorbent Assay (ELISA) applications. This antibody reacts with human,mouse samples. Cat.No. 10118-1-AP.
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Mouse polyclonal antibody raised against a full-length human CLDN1 protein. CLDN1 (NP_066924.1, 1 a.a. ~ 211 a.a) full-length human protein. (H00009076-B01P) - Products - Abnova
Sixty mutations of claudin 16 coding gene have been reported in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) patients. Recent investigations revealed that a highly conserved glycine-leucine-tryptophan (115G-L-W117) motif in the first extracellular segment (ESC1) of claudin 16 might be essential for stabilization of the appropriately folded ECS1 structure and conservation of normal claudin 16 function. However, neither missense nor nonsense mutation has ever been described in this motif. Our study aimed at identifying mutations in a Chinese patient with FHHNC and exploring the association between genotype and phenotype. A 33-year-old female presented with 4 years history of recurrent acute pyelonephritis without other notable past medical history. Her healthy parents, who aged 56 and 53 respectively, were second cousins, and her only sibling died from renal failure without definite cause at age 25. Renal ultrasound imaging demonstrated atrophic kidneys and bilateral
Tight junctions (TJs) are constructions indispensable to epithelial cells and are responsible for regulations of paracellular diffusion and maintenance of cellular polarity. interstitial tissues spaces. Located at the pinnacle of horizontal walls, TJs have both wall and barriers features. The barriers function represents a selectively permeable filtration system that adjusts paracellular diffusion of ions and solutes structured on charge and size, respectively (Gemstone, 1977 ). Barriers function is certainly firmly governed by a particular arranged of TJ protein, the claudins (Tsukita made up of a non-specific shRNA into MDCK II cells (brief hairpin non-specific control [shCtrl] cells). Specificities of RalA and RalB exhaustion had been ABT-263 decided by immunoblotting and immunofluorescence marking of endogenous protein; both RalB and RalA localised to the plasma membrane layer in subconfluent MDCK II cells, and this localization was untouched in shCtrl cells (Body 1B). In shRalA cells, ...
The tight junction regulates passage of molecules throuth the paracellular spaces. Occludin and claudins are the specific trancmembrance protains present at the tight junction and are believed to regulate the cell barrier functions. To examine the response of the tight junction to hyperosmotic solutions, Ⅰinvestigated the effects of hyperosmotic glycerol on function and protein expression of the tight junction in ECV304 cells. Cell cytotoxicity analysis showed that the high (10%) concentration of glcerol damaged 64.1% of the ECV304 cells (p<0.001), and this was confirmed morphologically. Treatment with 1%, 2% or 5% glyserol increased the paracellular permeability of fluorescein isothiocyanate (FITC) -labeled dextran by 4.7%, 18.7% and 29.4% (p<0.05), respectively. In addition, exposure to glycerol at any concentration strongly reduced the expression of occludin, whereas enpression of claudin-1 was affected very slightly. These results suggest that hyperosmotic glycerol would certainly ...
The ability to invade host tissues and metastasize is the major cause of cancer-related death. During tumor invasion, metastasizing cells disrupt normal cell-matrix adhesion and acquire an invasive phenotype. Claudins are adhesion proteins localized at tight junctions (TJs). Claudin-7 is a unique TJ membrane protein in that it has a stronger basolateral membrane distribution than that of apical TJs in epithelial cells. To study the basolateral function of claudin-7, claudin-7 gene silencing experiments were carried out in a lung cancer cell line using the lentivirus shRNA approach. We found that claudin-7 knockdown (KD) cells showed disrupted cell-matrix interactions. Consequently, when claudin-7 KD cells were plated on the uncoated glass surface, they were unable to attach to the glass and died the day after plating. In contrast, control cells adhered well and grew normally. Using immunofluorescent microscopy and biochemistry methods, we found that claudin-7 co-localized and ...
Tight junctions consist of a branching network of sealing strands of protein. Each strand is assembled from a series of transmembrane proteins(JAMs/Junctional Adhesion Molecules,Claudins and Occludin) embedded in plasma membranes. The extracellular domains join each other in tight junctions,whereas the intracellular domains are linked to peripheral membrane proteins,linking the transmembrane protein strands to actin cytoskeleton to create a functional network that plays a role in cellular processes. Each strand functions as an individual or linear barrie, therefore, the number of transmembrane protein strands is in relation with the degree of paracellular electrical resistance and impedance to solute flux in tight junctions[1]. Although other types of proteins are present at tight junctions, however, occludin and claudin are the major ones contributing to the structure of tight junctions. ...
The blood brain barrier (BBB) is a specialized barrier that renders the environment of the central nervous system (CNS) separate from other compartments of the body. The unique environment provided by the BBB enables the specialized activity of neurons; BBB breakdown is the result of pathologic conditions and leads to further neuronal dysfunction. The unique requirements of the CNS require the BBB to limit the free exchange of some solutes that would be freely exchanged through other anatomic compartments. The restriction of solute transport limits how fluids can transfer across the BBB.. The BBB is formed by endothelial cells that line cerebral micro vessels. 1 It restricts the entry of many substances dissolved in blood because of specialized tight junctions (TJ) between adjacent endothelial cells. BBB TJ are maintained by the interaction of specialized cytoskeleton and linking proteins not expressed in other endothelium, examples include : Claudins, occludins, and junctional adhesion ...
Looking for online definition of CLDN8 in the Medical Dictionary? CLDN8 explanation free. What is CLDN8? Meaning of CLDN8 medical term. What does CLDN8 mean?
Human CLDN7 partial ORF ( NP_001298, 31 a.a. - 81 a.a.) recombinant protein with GST-tag at N-terminal. (H00001366-Q01) - Products - Abnova
Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in differentiating keratinocytes and Langerhans cells in the epidermis. Our objective was to identify immunoreactive CLDN1 in human epidermal Langerhans cells and to examine the pattern of epidermal Langerhans cells in genetic human CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome]. Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies were analysed by confocal laser immunofluorescence microscopy and flow cytometry. Skin biopsy sections of two patients with NISCH syndrome were stained with an antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans cells and a subpopulation of keratinocytes from healthy skin were positive for CLDN1. The gross number and distribution of epidermal Langerhans cells of two patients with molecularly confirmed NISCH syndrome, however, was not grossly altered. Therefore, CLDN1 is unlikely to play a critical role in ...
In this study, we demonstrated (I) distinct expression patterns of five genes encoding for proteins involved in the formation of tight junctions in esophageal mucosa. In particular Claudin-1 in ERD and to lesser extent Claudin-2 was expressed at higher levels in patients with GERD. In contrast, ZO-1, ZO-2, and Occludin were not affected by the presence of GERD. (II) In general, altered gene expression of Claudin-1/-2 did not correlate with the degree of histomorphological changes in the esophageal mucosa of patients with GERD.. Tight junctions are composed of transmembrane proteins such as Occludin, 24 Claudins, several junctional adhesion molecules (JAMs) with different isoforms, E-Cadherin as well as cytosolic binding partners [43, 44]. The selection of the five genes studied was based on functional aspects. Occludin is critical for the formation of tight junctions in most tissues [45]. Claudin-1 is one of the numerous Claudins that seals intercellular space leading to higher barrier function ...
DESCRIPTION (provided by applicant): Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer metastasis and invasion. Role of adherent junction proteins have been studied extensively in cancer, however the role of tight junction proteins is less understood. Claudins are the recently identified tetraspanins, which are integral to the structure and function of tight junctions (TJs). Recent studies have shown changes in expression/cellular localization for claudins during tumorigenesis, however a cause and effect relationship has not been established. Here, we report a highly increased expression for claudin-1 in human primary colon carcinoma and metastatic tissues and cell lines derived from similar sources with relatively frequent nuclear localization. Furthermore, using genetic manipulations of claudin-1 expression in colon cancer cell lines, we demonstrate a role for claudin-1 in the regulation of epithelial to mesenchymal ...
In multicellular organisms, compartments with different compositions are separated by epithelia. Exchange of solutes between compartments can occur through (transcellular) or around (paracellular) the epithelial cells. Tight junctions between the cells form an ion-selective barrier across the paracellular route, and several human diseases involve a breakdown of these junctions. On p. 5109, Daniel Goodenough and colleagues report that the tight junction protein paracellin 1 (claudin-16) can modulate tight junction ion selectivity in the renal epithelial cell line LLC-PK1, which does not normally express this protein. When the authors express paracellin 1 in these cells, it localizes to the tight junctions and increases their permeability to Na+ but not to Cl- or Mg2+. Mutagenesis studies indicated that the extracellular loops of paracellin 1 are critical for this ion selectivity. Similar paracellin 1 mutations cause human familial hypomagnesemia with hypocalcinuria and nephrocalcinosis (FHHNC), ...
This effect appeared to be mediated primarily by the action of HGF on the cytoplasmic membrane plaque protein ZO-1. ZO-1 is a peripheral membrane protein localized to the tight junction complex in epithelial and endothelial cells. Anchoring of ZO-1 with the underlying cytoskeleton is required for localization of occludin and claudin in the tight junction. ZO-1, -2, and -3 contain three PDZ domains, one SH3 domain, and one guanylyl kinase-like domain (GuK). Through its GuK domains, ZO-1 binds directly to the carboxyl termini of claudins and occludin and may function as an adaptor at the cytoplasmic surface of the tight junction to recruit other proteins, including cytoskeletal and signaling molecules. 4 These components can form a huge macromolecular complex at the cytoplasmic surface of tight junctions and may be involved in the regulation of endothelial and epithelial cell polarization, proliferation, and differentiation. 4 As an adaptor, ZO-1 is a critical regulatory protein between occludin ...
Claudin 5 as a prominent TJ protein is a consistent feature between the BBB and blood-CSF barrier (Bill and Korzh, 2014). Here we have used this feature to create an in vivo model for real-time analysis of the development, structure and function of the BBB and CP by generating a transgenic zebrafish line that expresses EGFP under the claudin 5a promoter. The high homology and synteny with human, the conservation along the teleost lineage and the previous characterisation of Claudin 5a in zebrafish makes cldn5a a logical candidate (Abdelilah-Seyfried, 2010; Xie et al., 2010; Zhang et al., 2012).. We show that developmental expression of cldn5a:EGFP is restricted to, and starts in both CPs and the midline at 1 dpf, thereby narrowing down the previously shown whole-mount in situ hybridizations (Zhang et al., 2010). The presence of Claudin 5a at the CPs at 1 dpf coincides with the inflation of the ventricles (Zhang et al., 2010, 2012) and corroborates its role in this process. Claudin 5a is crucial ...
Objective Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag+ strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H. pylori modulates expression of the cancer-associated tight junction protein claudin-7.. ...
Read "Claudin-8 Expression in Renal Epithelial Cells Augments the Paracellular Barrier by Replacing Endogenous Claudin-2, The Journal of Membrane Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
TABLE-US-00004 TABLE 4 Cell and biological adhesion Fold Symbol Gene name Gene assignment change CLDN7 claudin 7 Involved in the formation of 2.74 tight junctions between epithelial cells PCDHB5 Protocadherin Member of the 3.32 beta-5 protocadherin beta gene cluster CLDN3 Claudin 3 Member of the claudin 3.93 family, is an integral membrane protein and a component of tight junction strands. CNTN6 contactin 6 Contactins mediate cell 3.09 surface interactions during nervous system development. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. PKHD1 polycystic kidney Localized predominantly at 3.38 and hepatic the disease 1 apical domain of polarized epithelial cells, suggesting it may be involved in the tubulogenesis and/or maintenance of duct-lumen architecture. PCDHB2 protocadherin The extracellular domains 2.94 beta 2 interact in a homophilic manner to specify differential cell-cell connections. CDH1 E-cadherin cell adhesion molecule 3.27 (epithelial) CX3CL1 hemokine ...
From NCBI Gene:. The product of this gene belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in this gene are the cause of hypomagnesemia renal with ocular involvement (HOMGO). HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]. From UniProt: ...
Familial Hypomagnesaemia with Hypercalciuria and Nephro-calcinosis (FHHN) is a rare disorder of calcium and magnesium paracellular transportation at TAL level
In this study, we have described a new biochemical assay that efficiently reconstitutes the endocytosis of E-cadherin using the AJ plasma membranes. We have found here that non-trans-interacting E-cadherin is constitutively endocytosed like integrin (ligand-independent endocytosis), that the formation of endocytosed vesicles of E-cadherin is clathrin dependent, and that E-cadherin, but not other CAMs at AJs and TJs including nectins, claudins, and occludin, is selectively sorted into the endocytosed vesicles. Recent cell-level studies using chemical inhibitors have shown that E-cadherin might be internalized by clathrin- or caveolin-dependent endocytosis (Le et al., 1999; Akhtar and Hotchin, 2001; Palacios et al., 2002; Thomsen et al., 2002; Paterson et al., 2003; Ivanov et al., 2003). However, the results obtained in this way are indirect and not substantial because the low resolution indirect immunofluorescence staining could only follow the appearance of E-cadherin in large vesicular ...
While growth factor-independent signaling and proliferation are well-established hallmarks of cancer, little is known regarding growth factor-independent changes in gene expression which occur downstream from oncogenes. The PI3K pathway is one of the most commonly misregulated signaling pathways in human cancers. Here, MCF10A cells expressing the two most common PI3K mutations, PIK3CA E545K and H1047R, were used to identify the repertoire of genes altered by oncogenic PI3K mutations following growth factor deprivation. This gene set most closely correlated with gene signatures from claudin-low and basal-like breast tumors, and categorical enrichment analyses suggested that NF-κB target genes were dramatically upregulated by these mutations. An IKKα inhibitor was used to identify the subset of PI3K-driven genes that is NF-κB dependent. Interestingly, virtually all of these NF-κB dependent genes were secreted proteins, suggesting a paracrine role for this gene set. Among these genes was IL-6, ...
Expression of CLDN4 (CPE-R, CPETR, CPETR1, hCPE-R, WBSCR8) in rectum tissue. Antibody staining with CAB002610 in immunohistochemistry.
The entire human body and its many compartments are shielded from their external environments by the barrier function of epithelial cell sheets. The paracellular barrier function of tight junctions (TJs) is critical for maintaining homeostasis in any multicellular organism, especially in the skin and internal organs and at the blood-brain barrier. One of the major components of TJs is a family of adhesive membrane proteins known as claudins. Several members of the claudin family are receptors for the bacterial toxin Clostridium perfringens enterotoxin. This toxin often causes food-borne illness both in humans and animals. Saitoh et al. crystallized a complex between the toxin and a claudin that reveals just how the toxin damages epithelial barriers (see the Perspective by Artursson and Knight).. Science, this issue p. 775; see also p. 716 ...
Blood-brain barrier (BBB) leakage plays a key role in cerebral ischemia-reperfusion injury. It is quite necessary to further explore the characteristic and mechanism of BBB leakage during stroke. We induced a focal cerebral ischemia model by transient middle cerebral artery occlusion in male rats for defining the time course of BBB permeability within 120 h following reperfusion and evaluate the specific role of tight junction (TJ) associated proteins claudin-5, occludin, and ZO-1 as well as protein kinase C delta (PKCδ) pathway in BBB leakage induced by reperfusion injury. We verified a bimodal increase in the permeability of the BBB following focal ischemia by Evans blue assay. Two peaks of BBB permeability appeared at 3 h and 72 h of reperfusion after 2 h focal ischemia, respectively. The leak at the endothelial cell was represented at the level of transmission electron microscopy. TTC staining results showed increased infarct size with time after cerebral ischemia reperfusion. The mRNA and ...
The protein encoded by this intronless gene belongs to the claudin family. Claudins are integral membrane proteins that are components of the epithelial cell tight junctions, which regulate movement of solutes and ions through the paracellular space. This protein is a high-affinity receptor for Clostridium perfringens enterotoxin (CPE) and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems. [provided by RefSeq, Sep 2013 ...
The tight junction protein claudin-1 (CLDN1) has been shown to be essential for hepatitis C virus (HCV) entry-the first step of viral infection. Due to the lack of neutralizing anti-CLDN1 antibodies, the role of CLDN1 in the viral entry process is poorly understood. In this study, we produced antibodies directed against the human CLDN1 extracellular loops by genetic immunization and used these antibodies to investigate the mechanistic role of CLDN1 for HCV entry in an infectious HCV cell culture system and human hepatocytes. Antibodies specific for cell surface-expressed CLDN1 specifically inhibit HCV infection in a dose-dependent manner. Antibodies specific for CLDN1, scavenger receptor B1, and CD81 show an additive neutralizing capacity compared with either agent used alone. Kinetic studies with anti-CLDN1 and anti-CD81 antibodies demonstrate that HCV interactions with both entry factors occur at a similar time in the internalization process. Anti-CLDN1 antibodies inhibit the binding of ...
Aim of this volume is to clarify the relationship between molecular structure and function of tight junction proteins, as well as their regulation and their role in diseases. Current research may form a basis for future diagnostic and therapeutic approaches to diseases which seem to have not much in common but are characterized by defects of organ barriers, like Crohns disease, renal hypertension, inner ear deafness, and cancerous diseases. Topics include the functions of distinct tight junction proteins as barrier or channel formers for solutes and water, characteristics of the tight junction in inflammatory bowel diseases, posttranslational modifications of tight junction proteins, the relation between renal tight junction proteins and blood pressure control, and the molecular structure of claudin-claudin interactions NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas.
Mouse monoclonal ZO1 tight junction protein antibody [mAbcam 61357] validated for WB, IP, Flow Cyt and tested in Human. Referenced in 2 publications and 5…
Occludin is an integral membrane protein, encoded by the OCLN gene, that is located at tight junctions. Tight junctions act as a physical barrier to prevent solutes and water from passing freely through the paracellular space. Occludin is also known as BLCPMG. It is known to interact with several cytoplasmic proteins via its C terminus, while its extracellular loops are thought to be involved in the regulation of paracellular permeability and cell adhesion. When occludin is expressed in cells that lack tight junctions, it is able to induce cell adhesion. Mutations in the OCLN gene are associated with an autosomal recessive neurologic disorder known as band-like calcification with simplified gyration and polymicrogyria (BLC-PMG).. ...
Occludin is an integral membrane protein, encoded by the OCLN gene, that is located at tight junctions. Tight junctions act as a physical barrier to prevent solutes and water from passing freely through the paracellular space. Occludin is also known as BLCPMG. It is known to interact with several cytoplasmic proteins via its C terminus, while its extracellular loops are thought to be involved in the regulation of paracellular permeability and cell adhesion. When occludin is expressed in cells that lack tight junctions, it is able to induce cell adhesion. Mutations in the OCLN gene are associated with an autosomal recessive neurologic disorder known as band-like calcification with simplified gyration and polymicrogyria (BLC-PMG).. ...
Mechanosensitive ion channels (MS channels) represent a diverse population of ion channels. Other membrane-associated proteins with different biophysical properties apart from ion channels, specialized cytoskeletal proteins, cell junction molecules and G-protein-coupled receptors and kinases, among many others are also considered mechanosensitive. MS channels integrate a variety of mechanical stimuli such as shear stress, tension, torsion, and compression and translate them into short-term effects (i.e., changes in ion concentrations and voltage) and long-term effects via changes in gene expression. ...
The tight junction (TJ) is a dynamic structure that is controlled, in part, by the activity of the cytoskeleton. It has become abundantly clear that, in the presence of Ca2+, assembly of the TJ is the result of cellular interactions that trigger a complex cascade of biochemical events that ultimatel …
Expression of CLDN7 (CEPTRL2, CPETRL2, Hs.84359) in testis tissue. Antibody staining with HPA014703 and CAB013063 in immunohistochemistry.
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Obat ketika masuk tubuh mengalami nasib yaitu: absorbsi, distribusi, metabolisme, dan ekskresi (ADME). Obat utamanya masuk ke dalam sel. Sebenarnya aliran senyawa melalui paraseluler bisa terjadi, namun ada halangan yaitu adanya tight junction, misal di SSP. Obat bisa ditransport secara pasif maupun aktif. Transport pasif artinya mengikuti gradien konsentrasi yaitu dari konsentrasi tinggi ke konsentrasi…
TY - PAT. T1 - Compositions and Methods for Enhancing Paracellular Permeability across Epithelial and Endothelial Barriers. AU - Thakker,Dhiren R.. AU - Ward,Peter D.. N1 - Status: published applicationnumber: 09/974,519 usclass: 514/75 ; 514/642; 514/76; 514/946 applicationnumber: 09/974,519. PY - 1800. Y1 - 1800. N2 - Compositions and methods for enhancing paracellular permeability at an absorption site in a subject are disclosed. The method includes: (a) administering an effective amount of a phospholipase C inhibitor to a subject at a time in which enhanced paracellular permeability is desired; and (b) enhancing paracellular permeability in the subject at the absorption site through the administering of the effective amount of the phospholipase C inhibitor. The disclosed compositions and methods provide enhanced absorption of a hydrophilic drug in a subject.. AB - Compositions and methods for enhancing paracellular permeability at an absorption site in a subject are disclosed. The method ...
Freeze-fracture replica images of TJs in neo-MDCK I (a), dCL2-MDCK I (b), and MDCK II cells (c). Cells (4 × 105 cells) were plated on 24-mm filters, cultured f
Epithelial layers are integral for many physiological processes and are maintained by intercellular adhesive structures. During disease, these structures can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis of many diseases. The present review focuses on the role of vesicle trafficking in regulation of TJs, in particular trafficking of the TJ protein occludin. We examine how endocytosis and endosomal recycling modulate occludin localization under steady-state conditions and during stimulated TJ disassembly. ...
The relationship between the molecular structure and function of tight junction proteins, as well as their regulation and their role in disease, is discussed.
CLDN20 - human gene knockout kit via CRISPR, 1 kit. |dl||dt|Kit Component:|/dt||dd|- |strong|KN205032G1|/strong|, CLDN20 gRNA vector 1 in |a href=http://www.origene.com/CRISPR-CAS9/Detail.
Restore optimal gut environment leads to great gut health with carbon rich alkaline liquid lignite extracts to strengthen tight junction cells
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TY - JOUR. T1 - Effect of cerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas. AU - Fallon, Michael B.. AU - Gorelick, Fred S.. AU - Anderson, James M.. AU - Mennone, Albert. AU - Saluja, Ashok. AU - Steer, Michael L.. PY - 1995/6. Y1 - 1995/6. N2 - Background/Aims: Cerulein-induced pancreatitis causes a rapid increase in pancreatic enzyme levels in serum and decreases in pancreatic duct secretion and interstitial edema. One mechanism to explain these early events is disruption of the actin tight junction paracellular seal of acinar and intralobular pancreatic duct cells. Methods: To examine the paracellular barrier of the proximal exocrine pancreas, rats were hyperstimulated with 5.0 μg · kg-1 · h-1 of cerulein. Actin was visualized with rhodamine phalloidin and by electron microscopy and tight junctions were visualized with antibodies to the tight-junction protein ZO-1. Paracellular permeability was measured by movement of horseradish peroxidase from interstitium ...
In the present study we identified a diverse group of Tcfap2c-regulated genes with established roles in blastocyst formation. These include genes that are important for TJ assembly (Cldn4, Cldn6, Tjp2, Tjp1), cell polarity (Pard6b) and fluid accumulation (Atp1b1, Aqp3). Claudin family members encode tetraspanin membrane proteins that serve crucial roles in TJ assembly and epithelial cell barrier function (Krause et al., 2008). In preimplantation embryos, disruption of Cldn4 and Cldn6 function via an inhibitory peptide impairs blastocyst development (Moriwaki et al., 2007). The TJ proteins Tjp1 and Tjp2 play an important role in connecting the actin skeleton with TJ complexes at the apical membrane (Schneeberger and Lynch, 2004). Embryos that lack Tjp1 or Tjp2 exhibit defects in blastocyst formation and/or undergo early embryonic lethality (Katsuno et al., 2008; Sheth et al., 2008). Likewise, in mouse preimplantation embryos the cell polarity regulator Pard6b is essential for blastocyst formation ...
The blood-brain barrier is located at the level of the brain blood capillaries. There are several components of the barrier.. Tight junctions. A key component of the blood-brain barrier is the tight junctions between endothelial cells in central nervous system capillary vessels that restricts the passage of solutes. At the interface between blood and brain, endothelial cells and associated astrocytes (type of glia) are stitched together by structures called "tight junctions." The tight junction is composed of smaller subunits, frequently dimers, that are transmembrane proteins such as occludin, claudins, junctional adhesion molecule (JAM), ESAM, and others. Each of these transmembrane proteins is anchored into the endothelial cells by another protein complex that includes zo-1 and associated proteins. The sealing together by tight junctions of the cells making up the walls of the vessels prevents water-soluble substances from freely passing between the cells and entering the fluid environment of ...
1. Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 30 normal subjects, 14 patients with minimal proteinuria and 23 patients with heavy proteinuria due to primary glomerulopathies. Seven patients with minimal change nephropathy were studied in relapse and remission.. 2. CPAm/CSAm exceeded 2.0 (range 2.1-6.1) in all normal subjects, indicating that the normal glomerular capillary wall possesses charge selectivity at the molecular size of amylase (molecular mass 56 kDa). 3. CPAm/CSAm was significantly lower in patients with heavy proteinuria than in normal subjects or patients with minimal proteinuria. CPAm/CSAm was low in patients with minimal change nephropathy in relapse and rose into the normal range with steroid-induced remission.. 4. These data suggest that heavy proteinuria in primary glomerulopathies is accompanied by loss of glomerular charge selectivity. Remission ...
Capillary endothelium Endothelial basement membrane Interstitial space Epithelial basement membrane Alveolar epithelium ( type I pneumocyte) (thick , upper - fluid & gas  On one side of alveolar septum  On the other side exchanging side) there is connective tissue and interstitial space (thin , down- gas exchange only) basement membranes are fused and there is a greatly restricted interstitial space 55 .    There are tight junctions on the epithelium of the upper side (passage of fluid from interstitial space to alveolus) There are loose junction on the endothelium of the upper side (passage of fluid from intravascular space to interstitial space) Pulmonary capillary permeability depends on the size & number of loose junctions 56 . 1. 2. Interstitial space is between periarteriolar and peribronchial connective tissue shit and between epithelium & endothelium basement membrane in alveolar septum The space has a progressively negative distal to proximal ΔP Negative ΔP increases ...
Open peer review is a system where authors know who the reviewers are, and the reviewers know who the authors are. If the manuscript is accepted, the named reviewer reports are published alongside the article. Pre-publication versions of the article and author comments to reviewers are available by contacting [email protected] All previous versions of the manuscript and all author responses to the reviewers are also available.. You can find further information about the peer review system here.. ...
To understand tissue morphogenesis and disease pathogenesis, ultimately we must understand what happens at the cellular and molecular levels. To do this, we use a number of techniques. To identify new protein-protein interactions important for establishing the machinery through which junctions carry out structural and signaling functions, we use in vitro biochemistry and a variety of protein interaction screens, including recently emerging Bio-ID proteomic approaches that allow for mapping nearest neighbors in cells and tissues in situ. How these protein interactions are regulated by post-translational modifications, including phosphorylation and protein methylation is also being uncovered through the use of mass spectrometry approaches.. To look at the importance of these protein interactions in cells, state-of-the-art optical imaging techniques are being employed. Fluorescently-tagged wild type and mutant desmosome and adherens junction molecules are tracked during intercellular junction ...
The precise regulation of intestinal epithelial TJs is crucial to maintaining barrier function between the luminal milieu and the internal environment. Recent studies have revealed an important role for Rho GTPases in regulating TJ structure/function (22, 29). In particular, TJ strand organization has been shown to be altered by constitutively active RhoA and Rac1 mutants (22) and inactivation of GTPases by C. difficile toxins is known to cause redistribution of occludin and ZO-1 from membrane microdomains or membrane rafts (32). As a result, we have further explored the mechanisms whereby paracellular permeability is influenced by this family of mediators and investigated whether the inactivation of a single GTPase (RhoA, Rac1, or Cdc42) has an effect on TJ distribution in such membrane rafts and whether TJ proteins involved in strand formation (such as claudin-1 and -2) are altered in this setting.. Using MDCK cell lines that express constitutively active or dominant-negative RhoA, Rac1, or ...
Nephrocalcinosis definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up now!
Background The mind endothelium is a key component of the blood brain barrier which is compromised following ischemia allowing infiltration of damaging immune cells and other inflammatory molecules into the brain. that IVIg prevented the down-regulation of tight junction proteins claudin 5 and occludin and the decline in anti-apoptotic proteins Bcl-2 and Bcl-XL caused by […]. ...
Health Categories: Gluten Sensitivity Probiotic/Microbiome Clinical Dose of Quercetin, Bioferrin, Turmeric and L-Alynyl Glutamine in an herbalomic support blend. Lab studies have demonstrated the ability of Quercetin to support the intestinal mucosa by up-regulating the tight junction protein claudin and down-regulatin
Huynh M, Clark R, Li J, et al. A case control analysis investigating risk factors and outcomes for nephrocalcinosis and renal calculi in neonates. J Pediatr Urol. 2017;13(4):3... ...
Sigma-Aldrich offers abstracts and full-text articles by [Ryan C Winger, Jennifer E Koblinski, Takashi Kanda, Richard M Ransohoff, William A Muller].
Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but imp
Tight junctions (TJs) are electron‐dense structures connecting the lateral membranes of adjacent epithelial or endothelial cells. They exert adhesive properties and stabilize homophilic cell-cell binding. TJs serve a dual role in controlling paracellular permeability and in maintaining cell polarity. These junctional structures are particularly well developed in regions of the vascular tree where permeability has to be restricted, e.g. in the brain microvasculature and in large arteries (Mitic and Anderson, 1998; Stevenson and Keon, 1998; Dejana et al., 2000). Little is known about the molecular basis for the intercellular adhesion of TJs, despite their eminent role in organ functioning. Different transmembrane proteins have been found to be located specifically at TJs. Occludin and the claudin family belong to the class of tetra‐span transmembrane proteins (Furuse et al., 1993, 1998a,b). Occludin is dispensable for TJ organization and adhesive properties (Saitou et al., 1998). In contrast, ...
As mentioned in our introduction, the availability of CPE-directed therapeutics could be helpful for ameliorating several CPE-associated medical conditions. A previous study had suggested that the drug mepacrine might be a candidate CPE therapeutic because the presence of this drug interferes with CPE-induced electrophysiologic activity in artificial lipid bilayers (24). However, that study did not distinguish whether mepacrine inactivates the CPE protein or instead interferes with some step in CPE action, i.e., whether this drug affects CPE binding, CPE pore formation, or CPE pore activity. Furthermore, it was specifically important to determine whether mepacrine is not only protective against CPE electrophysiologic activity in artificial membranes but also inhibits CPE-induced cytotoxicity in mammalian cells, where receptors are present and complex phenomena like membrane vesicle release occur (30).. Therefore, a first major contribution of the current study entailed demonstrating that ...
The next 3 papers are from the most recent ones in NDT. C. Gast first reports that "Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis". Next, L. Cosmai publishes a review "Onco-nephrology: a decalogue". Then PA Schytz et al. studied the "Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis". Finally, in a recent CKJ paper F Claverie-Martin reviews "Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis : clinical and molecular characteristics ...
NIH 1RO1-GM098584-01A1, for "Structure-function Relation of Connexin Disease Mutations." Principal investigator. Sept. 1, 2012 - Aug. 31, 2016; $109,468 per year. In this grant I investigate structural alterations in the N-termini of Connexin gap junction molecules in diseases such as deafness, fatal skin disease and neuropathy. I use NMR spectroscopy to produce structural data of these molecules, which are then analyzed with functional data showing alterations in gap junctions observed in these diseases. The structural and functional data may provide insight into the etiology of these diseases as well as molecular mechanistic information on gap junction assembly and gating. (Grants and Fellowships) ...
The capillary wall performs an important function by allowing nutrients and waste substances to pass across it. Molecules larger than 3 nm such as albumin and other large proteins pass through transcellular transport carried inside vesicles, a process which requires them to go through the cells that form the wall. Molecules smaller than 3 nm such as water, ions and gases cross the capillary wall through the space between cells in a process known as paracellular transport.[17] These transport mechanisms allow bidirectional exchange of substances depending on osmotic gradients and can be further quantified by the Starling equation.[18] Capillaries that form part of the blood-brain barrier however only allow for transcellular transport as tight junctions between endothelial cells seal the paracellular space.[19] Capillary beds may control their blood flow via autoregulation. This allows an organ to maintain constant flow despite a change in central blood pressure. This is achieved by myogenic ...
All of us in the business talk about the blood-brain barrier, but. . .no, Im not going to end this sentence with . . .none of us do anything about it,
Endothelium differentiates in response to tissue-specific signals; brain endothelium expresses tight junctions and transporters which are absent from other endothelia. The promoter of the tight junction protein occludin exhibited strong activity in a brain endothelial cell line, hCMEC/D3 but was inactive in lung endothelial cells. Expression of occludin in brain endothelium corresponded with binding of Sp3 to a minimal promoter segment close to the transcription-start site. However, in lung endothelium Sp-transcription factors did not bind to this site although they are present in the cell nucleus. In contrast, repression of occludin in lung endothelium was associated with the binding of YY1 to a remote site in the promoter region, which was functionally inactive in brain endothelium. The work identified a group of transcription factors including Sp3 and YY1, which differentially interact with the occludin promoter to induce expression of occludin in brain endothelium and repression in other ...
Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with ...
Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases. Vitamin A is a widely used food supplement although its mechanistic effect on intestinal structures is largely unknown. The goal of this study was to explore the mechanism by investigating the influence of vitamin A on the intestinal barrier function, represented by tight junctions. IPEC-J2 cells were differentiated on transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) was used as an indicator of monolayer integrity and paracellular permeability. Western blot and the reverse transcriptase-polymerase chain reaction were used to assess the protein and mRNA expression of tight junction proteins. Immunofluorescence microscopy was used to evaluate the localization and expression of tight junctions. Differentiated cells were treated with a vehicle control (Ctrl), ...
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Tight junctions (TJs) are essential for establishing a selectively permeable barrier to diffusion through the paracellular space between neighboring cells. TJs are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic plaque consisting of many different proteins that form large complexes. These are proposed to be involved in junction assembly, barrier regulation, cell polarity, gene transcription, and other pathways ...
Tight junctions (TJs) are essential for establishing a selectively permeable barrier to diffusion through the paracellular space between neighboring cells. TJs are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic plaque consisting of many different proteins that form large complexes. These are proposed to be involved in junction assembly, barrier regulation, cell polarity, gene transcription, and other pathways ...
Epithelial and endothelial cells (EC) are building paracellular barriers which protect the tissue from the external and internal environment. The blood-brain barrier (BBB) consisting of EC, astrocyte end-feet, pericytes and the basal membrane is responsible for the protection and homeostasis of the brain parenchyma. In vitro BBB models are common tools to study the structure and function of the BBB at the cellular level. A considerable number of different in vitro BBB models have been established for research in different laboratories to date. Usually, the cells are obtained from bovine, porcine, rat or mouse brain tissue (discussed in detail in the review by Wilhelm et al. 1). Human tissue samples are available only in a restricted number of laboratories or companies 2,3. While primary cell preparations are time consuming and the EC cultures can differ from batch to batch, the establishment of immortalized EC lines is the focus of scientific interest. Here, we present a method for establishing ...
1. What is the distance between the points (1, 4) and (4, 8)? I said Distance = 5 2. Find the slope between (1, 4) and (4, 8) I said 4/3 3. Are the expressions (4x+4)/4 and x+1 equivalent? I said Yes 4. Simplify (x+y)2 x2 + 2xy + y2 5. Is (x - y )2 = x2 - y2? No. It is ... ...
Note: The DUA should normally not be used if a funding agreement (i.e., a subcontract) is in place between UMBC and the other entity for the same project. The funding agreement should address data-sharing. Please consult with your Grants and Contracts Manager to ensure that the appropriate language has been included in the applicable funding agreement. If this DUA relates to current funding, please contact your OSP manager prior to completing this ...
It belongs to the group of claudins. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial ... Swisshelm K, Macek R, Kubbies M (2005). "Role of claudins in tumorigenesis". Adv. Drug Deliv. Rev. 57 (6): 919-28. doi:10.1016/ ... with the COOH termini of claudins". J. Cell Biol. 147 (6): 1351-63. doi:10.1083/jcb.147.6.1351. PMC 2168087 . PMID 10601346. ...
2004). "Expression patterns of claudins, tight junction adhesion molecules, in the inner ear". Hear. Res. 187 (1-2): 25-34. doi ... It belongs to the group of claudins. GRCh38: Ensembl release 89: ENSG00000157224 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... 2002). "Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments". J. Am. Soc ...
It belongs to the group of claudins. GRCh38: Ensembl release 89: ENSG00000171217 - Ensembl, May 2017 GRCm38: Ensembl release 89 ...
It belongs to the group of claudins. This gene encodes an integral membrane protein, which belongs to the claudin family. The ... 2000). "Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins". J. ...
It belongs to the group of claudins. It forms anion-selective paracellular channels and is localized mainly in kidney proximal ...
It belongs to the group of claudins. This gene encodes a member of the claudin family. Claudins are integral membrane proteins ... Poliak S, Matlis S, Ullmer C, Scherer SS, Peles E (2002). "Distinct claudins and associated PDZ proteins form different ... with the COOH termini of claudins". J. Cell Biol. 147 (6): 1351-63. doi:10.1083/jcb.147.6.1351. PMC 2168087 . PMID 10601346. ...
It belongs to the group of claudins. Claudins, such as CLDN7, are involved in the formation of tight junctions between ... 2000). "Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins". J. ...
It belongs to the group of claudins. This gene is involved in hearing. GRCh38: Ensembl release 89: ENSG00000213937 - Ensembl, ... 2004). "Expression patterns of claudins, tight junction adhesion molecules, in the inner ear". Hear. Res. 187 (1-2): 25-34. doi ... 2002). "Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments". J. Am. Soc ...
2000). "Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins". J. ... It belongs to the group of claudins. GRCh38: Ensembl release 89: ENSG00000156284 - Ensembl, May 2017 GRCm38: Ensembl release 89 ...
It belongs to the group of claudins. GRCh38: Ensembl release 89: ENSG00000177300 - Ensembl, May 2017 GRCm38: Ensembl release 89 ...
It belongs to the group of claudins. The protein encoded by this gene belongs to the claudin family of tight junction ...
It belongs to the group of claudins. This gene encodes a member of the claudin family. Claudins are integral membrane proteins ... 2000). "Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight ...
It belongs to the group of claudins. CLDN18 belongs to the large claudin family of proteins, which form tight junction strands ...
It belongs to the group of claudins. Claudin-19 has been implicated in magnesium transport. Claudins, such as CLDN19, are ...
2002). "Claudins create charge-selective channels in the paracellular pathway between epithelial cells". Am. J. Physiol., Cell ... It belongs to the group of claudins. Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/ ... 2002). "Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments". J. Am. Soc ... "Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins". Am. J. ...
2000). "Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins". J. ... It belongs to the group of claudins. GRCh38: Ensembl release 89: ENSG00000184697 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... 2003). "The renal segmental distribution of claudins changes with development". Kidney Int. 62 (2): 476-87. doi:10.1046/j.1523- ... 2002). "Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments". J. Am. Soc ...
It belongs to the group of claudins. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial ...
It belongs to the group of claudins. Members of the claudin protein family, such as CLDN2, are expressed in an organ-specific ... 2000). "Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins". J. ... 2004). "Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins". Proc. Natl. Acad ...
Khan, Niamat; Asif, Abdul R. (2015-01-01). "Transcriptional Regulators of Claudins in Epithelial Tight Junctions". Mediators of ...
"Transcriptional Regulators of Claudins in Epithelial Tight Junctions". Mediators of Inflammation. 2015: 1-6. doi:10.1155/2015/ ...
Claudins allow for Mg2+ transport via the paracellular pathway; that is, it mediates the transport of the ion through the tight ...
It belongs to a related family of proteins called claudins. The protein encoded by CLDN14 is an integral membrane protein and a ... Van Itallie CM, Gambling TM, Carson JL, Anderson JM (2005). "Palmitoylation of claudins is required for efficient tight- ...
Some claudins form tight junction-associated pores that allow paracellular ion transport. The tight junctions have a net ...
2004). "Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins". Proc. Natl. Acad ...
Colegio, O. R., Van Itallie, C. M., McCrea, H. J., Rahner, C., & Anderson, J. M. (2002). Claudins create charge-selective ... Nicholson, M., Lindsay, L. A., & Murphy, C. R. (2010). Ovarian hormones control the changing expression of claudins and ...
The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and ... A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against ... Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism ... suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified ...
The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ ... One of the major components of TJs is a family of adhesive membrane proteins known as claudins. Several members of the claudin ... The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the ...
Claudins and epithelial paracellular transport.. Van Itallie CM1, Anderson JM.. Author information. 1. Department of Medicine, ... Recent evidence shows that claudins, a large family (at least 24 members) of intercellular adhesion molecules, form the seal ... This evidence comes from the study of claudins expressed in cultured epithelial cell models, genetically altered mice, and ...
Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis. ... Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis. ...
The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been ... The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease ... and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins ... Keywords: Claudins; Clostridium perfringens enterotoxin; drug delivery; tight junction Claudins; Clostridium perfringens ...
Regulation of claudins by post-translational modifications and cell signaling cascades. In: Claudins, edited by Yu AS, ... Claudins in Human Kidney Diseases. The first inherited disorder of claudins to be identified was FHHNC.70 This autosomal ... Role of Claudins in the Aldosterone-Sensitive Distal Nephron. *Regulation of ASDN Claudins by Aldosterone and With-No-Lysine ... Expression of Claudins in the Kidney. Most claudins are expressed in the renal tubule. Each segment and cell expresses multiple ...
Rabbit polyclonal antibodies were produced against peptides from claudins 2 through 5. The distribution of individual claudins ... Claudins have very different expression patterns among and within gastrointestinal tissues. We propose these patterns underlie ... Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut.. ... and the finding that some claudins can be junctional, lateral, or show a gradient in junctional vs. lateral localization along ...
ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation.. Umeda K1, Ikenouchi J ... ZO-1 and ZO-2 are major PDZ-domain-containing TJ proteins and bind directly to claudins, yet their functional roles are poorly ... When exogenously expressed in 1(ko)/2(kd) cells, ZO-1 and ZO-2 were recruited to junctional areas where claudins were ... Formation of tight junction (TJ) strands, which are crucial for this barrier, involves the polymerization of claudins, TJ ...
not a shop Claudins: Methods while we focus you in to your property Y. The Web request that you received is only a responding ... The shop Claudins: Methods is on the Deep gala of the Warwalks by the Wasp-kinden bunch. walked-with-purpose of the Apt argues ... shop Claudins: knows near, non-critical, and provides us help you better! challenge a website to destroy a s plan. age agents 1 ... re-equip shop Claudins: Methods and across the something. That accepted to teach a mass teacher. But it has back a hundred ...
Celiac.com 03/15/2010 A team of researchers recently set out to investigate mucosal expression of claudins 2, 3 and 4 in the ... Mucosal Expression of Claudins 2, 3 and 4 in Proximal and Distal Part of Duodenum in Children with Celiac Disease ... Mucosal Expression of Claudins 2, 3 and 4 in Proximal and Distal Part of Duodenum in Children with Celiac Disease ... Mucosal Expression of Claudins 2, 3 and 4 in Proximal and Distal Part of Duodenum in Children with Celiac Disease ...
... for the expression of brain endothelial specific claudins-3 and -12. Findings: hCMEC/D3 cells express claudins-3 and -12. ... Expression and localization of claudins-3 and -12 in transformed human brain endothelium.. Fluids and barriers of the CNS, 9 p ... blood brain barrier (BBB); hCMEC/D3; claudins; tight junction; statins. Academic Unit/School:. Faculty of Science, Technology, ... Expression and localization of claudins-3 and -12 in transformed human brain endothelium ...
Figure 7. Claudins expressed in the thin ascending limb of Henle. In addition to claudin-8 (Figure 3), claudin-3 and -4 were ... B) Claudins expressed in the collecting duct. In addition to claudin-8 (Figure 3), claudin-3 and -4 were concentrated at TJ of ... Figure 6. Claudins expressed in the thin descending limb of Henle. Only claudin-2 was detected in the thin descending limbs of ... Claudins, with molecular masses of approximately 23 kD, comprise a multigene family consisting of ,20 members (3,10-12). When ...
Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells.: The neonatal proximal tubule has a lower ... Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells.. Authors * Sas, David ... We transfected claudins 6 and 9 into Madin-Darby canine kidney II (MDCK II) cells and performed electrophysiological studies to ... Expression of claudins 6 and 9 resulted in an increased transepithelial resistance, decreased chloride permeability, and ...
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... American Journal of Clinical Pathology 2007 Jun;127(6):928-37. [Link] ... We analyzed the diagnostic role of claudins in effusion cytology in 325 effusions, including 218 ovarian, 49 breast, 15 ... Reactive mesothelial cells rarely expressed claudins. Claudin-7 expression was higher in ovarian than in breast adenocarcinoma ...
... a significant number of claudins form channels across TJs which feature selectivity for cations (claudins 2, 10b, and 15), ... Claudins in cancer biology. Curr Top Membr 65: 293‐333, 2010. 258.. Van Deurs B, Koehler JK. Tight junctions in the choroid ... The claudins. Genome Biol 10: 235.1‐235.7, 2009. 146.. Lemmers C, Michel D, Lane‐Guermonprez L, Delgrossi MH, Médina E, Arsanto ... C) Model of cis and trans interactions between the claudins 1, 2, 3, 5, and 12 and working hypothesis for TJ assembly. Step 1 ...
... for the expression of brain endothelial specific claudins-3 and -12. hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is ... Expression and localization of claudins-3 and -12 in transformed human brain endothelium. *Anja Schrade1,7. , ... The cells express endothelial specific and TJ markers including claudins-1 and -5 [8, 9]. The aim of the present study was to ... Like other claudins, it is regulated by post-translational modifications, a possible reason for the higher molecular weight ...
Claudins This volume of Current Topics in Membranes focuses on Membrane Protein Crystallization, beginning with a review of ...
20] that claudins have the potential to interact with MT1-MMP to activate MMP-2, suggest that claudins may increase MMP ... Extra-junctional claudins have been traditionally attributed to storage and mobilization of claudins to and from the tight ... Although it is still unclear how claudins may promote cell motility, it is becoming clear that claudins are indeed playing an ... Claudins -3, -4 and -7 are often present in breast [6-8], ovarian [9-11], and endometrial [12, 13] tumors and are often ...
Keywords: claudins; colorectal cancer; c-kit; claudin-3; c-Jun N-terminal kinase; activator protein-1 claudins; colorectal ...
... from the 24 known claudins, only claudins-1, -8, -10, -11, and -16 have been detected in salivary glands. These claudins (i.e ... Claudins. Claudins are members of a multigene family, with , 24 members in humans/rodents [61], presenting a unique tissue ... K. Turksen and T.-C. Troy, "Barriers built on claudins," Journal of Cell Science, vol. 117, no. 12, pp. 2435-2447, 2004. View ... S. Tsukita and M. Furuse, "The structure and function of claudins, cell adhesion molecules at tight junctions," Annals of the ...
Claudins are the major components of tight-junction strands in the TAL, where the reabsorption of magnesium occurs. [14, 15] ...
Numerous proteins were shown to be co-enriched with the CPE-binding claudins, but there are no indications (except for claudins ... The interaction of several claudins with Clostridium perfringens enterotoxin (CPE) has been exploited for an affinity-based ... Immunoblotting and mass spectrometry (MS) experiments demonstrate strong enrichment of the CPE-binding claudins -3, -4 and -7, ... CPE116-319 provides an efficient tool for single step enrichment of different claudins from cell lysates. ...
Claudins * Receptors, Estrogen * Receptors, Progesterone * ErbB Receptors Grant support * P30 ES010126/ES/NIEHS NIH HHS/United ...
  • Claudins are thought to polymerize to form continuous strands along the lateral membrane of one cell while the extracellular domains of claudins on adjacent cells bridge the paracellular space to interact with each other, much like the teeth of a zipper. (asnjournals.org)
  • When each claudin species or occludin was overexpressed in mouse L fibroblasts, claudin molecules, but not occludin, were polymerized within the plasma membranes to reconstitute paired TJ strands, indicating that claudins are major structural components of TJ strands ( 13 ). (asnjournals.org)
  • We examined the expression pattern of claudins, the major components of TJ strands, in these cells: claudin-1 and -4 were expressed both in MDCK I and II cells, whereas the expression of claudin-2 was restricted to MDCK II cells. (nih.gov)
  • The effect of single amino acid substitutions of the second ECL of Cld5 were studied in cells expressing various other endogenous claudins except Cld5. (hu-berlin.de)
  • The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. (mdpi.com)
  • Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. (mdpi.com)
  • A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. (mdpi.com)
  • A potential function for claudins not localized within tight junction structures can also be supported by the observation that during tumor progression, where disruption and loss of tight junction structures is a hallmark characteristic, certain claudin subtypes are distinctly expressed. (biomedcentral.com)
  • In the proximal tubule, claudins have a role in the bulk reabsorption of salt and water. (asnjournals.org)
  • Celiac.com 03/15/2010 - A team of researchers recently set out to investigate mucosal expression of claudins 2, 3 and 4 in the proximal and distal parts of duodenum in children with celiac disease. (celiac.com)
  • We have previously described the presence of two claudin isoforms, claudins 6 and 9, in the neonatal proximal tubule and subsequent reduction of these claudins during postnatal maturation. (mysciencework.com)
  • When NZO-1 was forcibly recruited to lateral membranes and dimerized, claudins were dramatically polymerized. (nih.gov)
  • Our findings demonstrate that claudin overexpression studies measure the combined effect of alterations in both endogenous and exogenous claudins, thus explaining the dependence of the phenotype on the host cell line. (deepdyve.com)
  • The investigation of claudins promises to reveal novel fundamental insights into the pathogenesis of many diseases, including acute kidney injury, salt-sensitive hypertension and kidney stone disease. (kumc.edu)
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  • Structural Basis of a Key Factor Regulating the Affinity between the Zonula Occludens First PDZ Domain and Claudins. (nih.gov)