Treatment of chemotherapy-resistant human ovarian cancer xenografts in C.B-17/SCID mice by intraperitoneal administration of Clostridium perfringens enterotoxin.
Ovarian cancer remains the most lethal gynecologic malignancy in the United States. Although many patients with advanced-stage disease initially respond to standard combinations of surgical and cytotoxic therapy, nearly 90% develop recurrence and inevitably die from the development of chemotherapy-resistant disease. The discovery of novel and effective therapy against chemotherapy-resistant/recurrent ... More
Defining desmosomal plakophilin-3 interactions.
AuthorsBonné S, Gilbert B, Hatzfeld M, Chen X, Green KJ, van Roy F
JournalJ Cell Biol
PubMed ID12707304
'Plakophilin 3 (PKP3) is a recently described armadillo protein of the desmosomal plaque, which is synthesized in simple and stratified epithelia. We investigated the localization pattern of endogenous and exogenous PKP3 and fragments thereof. The desmosomal binding properties of PKP3 were determined using yeast two-hybrid, coimmunoprecipitation and colocalization experiments. To ... More
Functional characterization and localization of a gill-specific claudin isoform in Atlantic salmon.
AuthorsEngelund MB, Yu AS, Li J, Madsen SS, Færgeman NJ, Tipsmark CK
JournalAm J Physiol Regul Integr Comp Physiol
PubMed ID21975646
'Claudins are the major determinants of paracellular epithelial permeability in multicellular organisms. In Atlantic salmon (Salmo salar L.), we previously found that mRNA expression of the abundant gill-specific claudin 30 decreases during seawater (SW) acclimation, suggesting that this claudin is associated with remodeling of the epithelium during salinity change. This ... More
Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation.
'Claudins are a family of integral membrane proteins of the tight junction that are thought to participate in the permeation of solutes across epithelia via the paracellular pathway. Claudin-8 is expressed in the distal renal tubule, which has a characteristically low passive permeability to monovalent cations. To test the hypothesis ... More
Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment.
AuthorsIvanov AI, Nusrat A, Parkos CA,
JournalMol Biol Cell
PubMed ID14528017
'The adherens junction (AJ) and tight junction (TJ) are key regulators of epithelial polarity and barrier function. Loss of epithelial phenotype is accompanied by endocytosis of AJs and TJs via unknown mechanisms. Using a model of calcium depletion, we defined the pathway of internalization of AJ and TJ proteins (E-cadherin, ... More
Differences in claudin synthesis in primary cultures of acinar cells from rat salivary gland are correlated with the specific three-dimensional organization of the cells.
'Tight junctions are essential for the maintenance of epithelial cell polarity. We have previously established a system for the primary culture of salivary parotid acinar cells that retain their ability to generate new secretory granules and to secrete proteins in a signal-dependent manner. Because cell polarity and cell-cell adhesion are ... More
Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.
AuthorsRaiko L, Siljamäki E, Mahoney MG, Putaala H, Suominen E, Peltonen J, Peltonen S,
JournalExp Dermatol
PubMed ID22639968
'Mutations in the ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 cause Hailey-Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis. We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was down-regulated with the small inhibitory RNA (siRNA) method. SiRNA inhibition significantly down-regulated the SPCA1 ... More
Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium.
AuthorsAcharya P, Beckel J, Ruiz WG, Wang E, Rojas R, Birder L, Apodaca G,
JournalAm J Physiol Renal Physiol
PubMed ID15068973
'In mammals, the bladder stores urine without permitting the passage of urine contents into the bloodstream, a function, in part, of the uroepithelial-associated tight junction complex. The protein constituents that make up this high-resistance barrier in the bladder are currently unknown, although the claudins, a multigene family, are thought to ... More
Distribution of tight junction proteins in adult human salivary glands.
AuthorsMaria OM, Kim JW, Gerstenhaber JA, Baum BJ, Tran SD
JournalJ Histochem Cytochem
PubMed ID18765838
'Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to ... More
Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells.
AuthorsYu AS, McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Lynch RD, Schneeberger EE,
JournalAm J Physiol Cell Physiol
PubMed ID15689410
The function of occludin (Occ) in the tight junction is undefined. To gain insight into its role in epithelial cell biology, occludin levels in Madin-Darby canine kidney II cells were suppressed by stably expressing short interfering RNA. Suppression of occludin was associated with a decrease in claudins-1 and -7 and ... More
Inducible expression of Snail selectively increases paracellular ion permeability and differentially modulates tight junction proteins.
AuthorsCarrozzino F, Soulié P, Huber D, Mensi N, Orci L, Cano A, Féraille E, Montesano R,
JournalAm J Physiol Cell Physiol
PubMed ID15930145
Constitutive expression of the transcription factor Snail was previously shown to trigger complete epithelial-mesenchymal transition (EMT). The aim of this study was to determine whether inducible expression of Snail could modify epithelial properties without eliciting full mesenchymal conversion. For this purpose, we expressed mouse Snail (mSnail) cDNA in Madin-Darby canine ... More
Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms.
AuthorsBruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A,
JournalJ Immunol
PubMed ID14634132
It is well known that inflammatory conditions of the intestinal mucosa result in compromised barrier function. Inflammation is characterized by an influx into the mucosa of immune cells that influence epithelial function by releasing proinflammatory cytokines such as IFN-gamma and TNF-alpha. Mucosal barrier function is regulated by the epithelial apical ... More
Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity.
AuthorsAgarwal R, D'Souza T, Morin PJ,
JournalCancer Res
PubMed ID16103090
Claudin proteins form a large family of integral membrane proteins crucial for tight junction formation and function. Our previous studies have revealed that claudin-3 and claudin-4 proteins are highly overexpressed in ovarian cancer. To clarify the roles of claudins in ovarian tumorigenesis, we have generated human ovarian surface epithelial (HOSE) ... More
Claudins create charge-selective channels in the paracellular pathway between epithelial cells.
AuthorsColegio OR, Van Itallie CM, McCrea HJ, Rahner C, Anderson JM,
JournalAm J Physiol Cell Physiol
PubMed ID12055082
Epithelia separate tissue spaces by regulating the passage of ions, solutes, and water through both the transcellular and paracellular pathways. Paracellular permeability is defined by intercellular tight junctions, which vary widely among tissues with respect to solute flux, electrical resistance, and ionic charge selectivity. To test the hypothesis that members ... More
Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells.
AuthorsPrasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE,
JournalLab Invest
PubMed ID16007110
Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along ... More
Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture.
AuthorsColegio OR, Van Itallie C, Rahner C, Anderson JM,
JournalAm J Physiol Cell Physiol
PubMed ID12700140
Tight junctions (TJs) regulate paracellular permeability across epithelia and vary widely in their transepithelial electrical resistance (TER) and charge selectivity. The claudin family of transmembrane proteins influences these properties. We previously reported that claudin-4 increased TER approximately 300% when expressed in low-resistance Madin-Darby canine kidney (MDCK) II cells and decreased ... More
Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin.
AuthorsHintsala HR, Siponen M, Haapasaari KM, Karihtala P, Soini Y,
Journal
PubMed ID24294371
Claudins are tight junction proteins regulating the paracellular permeability of cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a sample set consisting of a total of 93 cases representing normal skin, actinic keratoses and squamous cell carcinomas of the skin. There were ... More
Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1.
AuthorsFang X, Neyrinck AP, Matthay MA, Lee JW,
JournalJ Biol Chem
PubMed ID20554518
Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) ... More
Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal physiology and hypertension.
AuthorsKahle KT, Macgregor GG, Wilson FH, Van Hoek AN, Brown D, Ardito T, Kashgarian M, Giebisch G, Hebert SC, Boulpaep EL, Lifton RP,
JournalProc Natl Acad Sci U S A
PubMed ID15465913
Paracellular ion flux across epithelia occurs through selective and regulated pores in tight junctions; this process is poorly understood. Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia. Whereas WNK4 is known to regulate several transcellular transporters and channels involved in NaCl and ... More
Cultured monolayers of the dog jejunum with the structural and functional properties resembling the normal epithelium.
AuthorsWeng XH, Beyenbach KW, Quaroni A,
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID15550553
The development of a culture of the normal mammalian jejunum motivated this work. Isolated crypt cells of the dog jejunum were induced to form primary cultures on Snapwell filters. Up to seven subcultures were studied under the electron microscope and in Ussing chambers. Epithelial markers were identified by RT-PCR, Western ... More
Enhanced immunohistochemical resolution of claudin proteins in glycolmethacrylate-embedded tissue biopsies.
AuthorsCollins JE, Kirk A, Campbell SK, Mason J, Wilson SJ,
JournalMethods Mol Biol
PubMed ID21717371
There are a number of disadvantages with conventional tissue immunohistochemistry for accurate -localisation of claudin proteins. Traditionally, tissue cryopreservation or formaldehyde fixation with wax embedding is utilised prior to sectioning and antibody localisation. Wax embedding gives better morphological preservation than frozen tissue, but the required use of chemical cross-linking fixatives ... More
Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.
AuthorsDíaz-Coránguez M, Segovia J, López-Ornelas A, Puerta-Guardo H, Ludert J, Chávez B, Meraz-Cruz N, González-Mariscal L,
JournalPLoS One
PubMed ID23637756
Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned ... More
Functional ESCRT machinery is required for constitutive recycling of claudin-1 and maintenance of polarity in vertebrate epithelial cells.
AuthorsDukes JD, Fish L, Richardson JD, Blaikley E, Burns S, Caunt CJ, Chalmers AD, Whitley P
JournalMol Biol Cell
PubMed ID21757541
Genetic screens in Drosophila have identified regulators of endocytic trafficking as neoplastic tumor suppressor genes. For example, Drosophila endosomal sorting complex required for transport (ESCRT) mutants lose epithelial polarity and show increased cell proliferation, suggesting that ESCRT proteins could function as tumor suppressors. In this study, we show for the ... More