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PubMed1993

Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers.

The mechanisms whereby enteropathogenic Escherichia coli (EPEC) causes diarrhea remain undefined. We found that EPEC caused a decrease in transepithelial electrical resistance across polarized monolayers of Caco-2 and MDCK epithelial cells. This occurred approximately 6 to 10 h after bacterial addition and was reversible if the monolayers were treated with tetracycline or gentamicin. Although significant alterations in host actin occurred beneath adherent EPEC, actin filaments supporting tight junctions were not noticeably affected in the epithelial cells, nor was the distribution of ZO-1, a tight junction protein. Despite the decrease in transepithelial electrical resistance, EPEC did not cause an increase in [3H]inulin penetration across MDCK monolayers. Unlike in the parental strain, mutations in any loci involved in adherence or formation of attaching and effacing lesions were unable to cause a decrease in transepithelial resistance. These data indicate that EPEC causes a decrease in transepithelial electrical resistance by disrupting a transcellular (intracellular) pathway rather than by disrupting intercellular tight junctions (paracellular) and that these disruptions occur only when attaching and effacing lesions are formed.

Actins↗
PubMed1991

Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier.

The demonstration of 125I-labelled atrial natriuretic factor (ANF)-binding sites on choroid plexus suggests a physiological role of ANF on the blood-cerebrospinal fluid barrier. This ultrastructural study was undertaken to determine whether ANF (0.5 microgram) alters the permeability of rat blood-cerebrospinal fluid barrier under steady states. Horseradish peroxidase (HRP) was used as a marker of protein permeability and ionic lanthanum as a marker of ionic permeability. HRP was not observed in the walls of choroid plexus vessels of control rats at 3 or 6 min, while at 12 min HRP was present in vessel walls and occasionally in continuity in the adjacent intercellular space between choroidal epithelial cells. In ANF-treated rats, HRP was observed in vessel walls and in the intercellular space between the choroidal epithelial cells up to the apical tight junctions at 3 min, indicating an accelerated passage of tracer. Although HRP was never observed beyond the apical tight junctions in control or test animals, at 6 min test rats showed ionic lanthanum within these junctions in focal areas and in continuity in the adjacent ventricular cavity. These studies demonstrate that ANF causes accelerated passage of both HRP and ionic lanthanum from blood into choroid plexuses with passage of ionic lanthanum into the ventricular cavity through the apical tight junctions of choroidal epithelial cells. The latter is in keeping with the known function of ANF in regulating water and electrolyte fluxes.

Animals↗
PubMed1983

Changes in intercellular junctions. II. Modulation in embryonic chick liver in vitro by cytosine arabinoside and dexamethasone.

We have used an in vitro model to investigate the relationship between cell proliferation, cell maturation, and intercellular junctional changes that are seen during normal liver development. Chick liver fragments of embryonic stages 21, 28, and 39 were grown in organ culture in Medium 199 with 10% bovine serum albumin for 24 hr. Concurrent cultures were treated with cytosine arabinoside (ara-c, 20 micrograms/ml) to inhibit cell proliferation or with dexamethasone (2 microns/ml) to promote cell maturation. Control and treated liver cultures were analyzed using autoradiography to determine labeling index and quantitative computer graphic analysis of freeze-fracture micrographs to evaluate junctional changes. Explants treated with ara-c had a near zero labeling index. Those from embryonic stage 21 showed a 4-fold increase in tight junctional area, while those from embryonic stage 28 showed a 2.5-fold increase in tight junctional area and a 5-fold increase in gap junctional area. In liver of embryonic stage 39, junctional area increased, and conformation of junctions took on the typical form seen in the liver of the hatched chick. Thus high mitotic activity appears to disrupt cell junctions, reducing the amount of junctions present and causing pleomorphic configurations. Junctional area could also be modified with no change in mitotic activity by treatment with dexamethasone. Stage 28 embryo livers in culture with dexamethasone showed a 4-fold increase in the amount of tight junctions with no change in the amount of gap junctions. Some major findings based on these age-dependent responses are (1) if mitosis is blocked in young embryonic stages when proliferation is high, intercellular junctions tend to increase in amount, and to be more mature in configuration; (2) if maturation is stimulated with no change in proliferation, those junctions which normally increase with differentiation will increase in amount; and (3) it is possible to produce a change in the amount of one junctional type without affecting the other. Therefore the amount of cell surface occupied by junctions at any given time seems to depend on both the pattern of synthetic activity in the cell and the degree to which cell to cell contacts are stable and undisrupted by mitotic activity.

Animals↗
PubMed1993

Cholestatic potentials of alpha-naphthylisothiocyanate (ANIT) and beta-naphthylisothiocyanate (BNIT) in the isolated perfused rat liver.

Previous studies in rats have shown that a single oral dose of alpha-naphthylisothiocyanate (ANIT), but not the regioisomer beta-naphthylisothiocyanate (BNIT), results in intrahepatic cholestasis. The present studies were designed to evaluate the intrinsic cholestatic potential of ANIT and BNIT in the isolated perfused rat liver. Livers from male Sprague-Dawley rats (300-450 g) were isolated and perfused with Krebs-Henseleit buffer supplemented with 50 microM taurocholate and ANIT or BNIT (0, 5, 15 or 50 microM). Rates of bile flow, bile acid uptake and bile acid excretion were monitored for up to 70 min. Permeability of tight junctions also was evaluated. At concentrations of 5 microM, neither ANIT nor BNIT altered hepatobiliary function or tight junction permeability. In contrast, perfusion with 50 microM ANIT or BNIT for 35 min resulted in decreases in bile flow rates of 19 +/- 8 and 13 +/- 4%, respectively. After 70 min of perfusion with ANIT or BNIT, rates of bile flow were decreased by 78 +/- 5 and 71 +/- 4%, respectively. Bile acid excretion also was decreased following perfusion with 50 microM ANIT or BNIT. Perfusion with 50 microM ANIT or BNIT decreased bile acid uptake by 51 +/- 13 and 46 +/- 6%, respectively, at 60 min. Bile/plasma (B/P) ratios of [3H]sucrose were not affected by ANIT or BNIT at any time during perfusion, indicating that changes in bile flow and bile acid excretion in the isolated perfused liver were not associated with increased hepatocyte tight junction permeability. These data demonstrate that the direct portal infusion of a 50 microM concentration of either ANIT or BNIT produced marked decreases in bile flow, indicating that these isomers have a comparable intrinsic cholestatic potential in the isolated perfused liver.

1-Naphthylisothiocyanate↗
PubMed2001

Down-regulation of occludin expression in astrocytes by tumour necrosis factor (TNF) is mediated via TNF type-1 receptor and nuclear factor-kappaB activation.

Tight junctions form the diffusion barrier of brain microcapillary endothelial cells and support cell polarity. Also astrocytes express tight junction components such as occludin, claudin-1, ZO-1 and ZO-2, but do not establish a permeability barrier. However, little is known about the function and regulation of these molecules in astrocytes. We studied the impact of tumour necrosis factor (TNF) on occludin and ZO-1 expression in astrocytes. TNF decreased occludin, but not ZO-1 expression. In brain microcapillary endothelial cells, as well as in epithelial cells, occludin expression was not influenced by TNF. Removal of TNF from astrocytes restored the basal level of occludin. Down-regulation was inhibited by caffeic acid phenethyl ester, a specific inhibitor of nuclear factor-kappaB (NF-kappaB) activation. Exposure of astrocytes isolated from mice deficient in either TNF type-1 receptor (TNFR1), TNF type-2 receptor (TNFR2), or both, respectively, revealed that down-regulation was mediated entirely by TNFR1. ZO-1, which can interact with occludin, was found to co-precipitate connexin43, but not occludin. These findings demonstrate that TNF selectively down-regulates occludin in astrocytes, but not in cells forming established tight junctions, through TNFR1 and suggest that NF-kappaB is involved as a negative regulator.

Animals↗
PubMed1989

An electrophysiological freeze fracture assessment of cadmium nephrotoxicity in vitro.

Human proximal tubule cell cultures exposed to doses of cadmium chloride (CdCl2) between 0.05 microgram/ml and 0.5 microgram/ml exhibited alterations in cell membrane structure and transport function. At these Cd concentrations, cell numbers were not significantly altered from control values in either nonreplicating confluent, or actively replicating subconfluent cultures. Transmission electron microscopy revealed few alterations in cultures treated with 0.05 microgram/ml Cd. Tight junctions were intact; organelles and myeloid body formation appeared normal. Freeze fracture analysis confirmed the integrity of the tight junctions as well as increased numbers of vesicles or pits along the lateral cell membrane, indicating increased endocytotic activity. Cells exposed to 0.1 microgram/ml Cd were characterized by decreased numbers of microvilli and inhibited myeloid body formation. Cd doses of 0.5 micrograms/ml elicited nuclear chromatin condensation, fragmented sealing strands in 5 to 10% of the tight junction profiles, sparse microvilli, and inhibited myeloid body formation. Electrophysiologic assessments of transport function by Ussing chamber analysis revealed decreases in transepithelial potentials for all three concentrations, with significant differences at Cd concentrations of 0.5 to 0.1 micrograms/ml. Cells treated with 0.5 micrograms/ml Cd also exhibited slight decreases in electrical resistance, consistent with the minimal fragmentation of sealing strands observed in freeze fracture replicas. Resistance in cultures treated with 0.1 or 0.05 micrograms/ml Cd remained within control values and indicated that drops in potential difference and short circuit current in these cells reflected true alterations in ion transport.

Biological Transport↗
PubMed2006

Transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers: Influence of size, charge and fluorescent labeling.

PURPOSE: To investigate the transport of poly(amidoamine) (PAMAM) dendrimers with positive, neutral and negatively charged surface groups across Caco-2 cell monolayers. METHODS: Cationic PAMAM-NH2 (G2 and G4), neutral PAMAM-OH (G2), and anionic PAMAM-COOH (G1.5-G3.5) dendrimers were conjugated to fluorescein isothiocyanate (FITC). The permeability of fluorescently labeled PAMAM dendrimers was measured in the apical-to-basolateral direction. 14C-Mannitol permeability was measured in the presence of unlabeled and FITC labeled PAMAM dendrimers. Caco-2 cells were incubated with the dendrimers followed by mouse anti-occludin or rhodamine phalloidin, and visualized using confocal laser scanning microscopy to examine tight junction integrity. RESULTS: The overall rank order of PAMAM permeability was G3.5COOH > G2NH2 > G2.5COOH > G1.5COOH > G2OH. 14C-Mannitol permeability significantly increased in the presence of cationic and anionic PAMAM dendrimers with significantly greater permeability in the presence of labeled dendrimers compared to unlabeled. PAMAM dendrimers had a significant influence on tight junction proteins occludin and actin, which was microscopically evidenced by disruption in the occludin and rhodamine phalloidin staining patterns. CONCLUSIONS: These studies demonstrate that enhanced PAMAM permeability is in part due to opening of tight junctions, and that by appropriate engineering of PAMAM surface chemistry it is possible to increase polymer transepithelial transport for oral drug delivery applications.

Actins↗
PubMed1978

Taste buds in the vallate papillae of the rat studied with freeze-fracture preparation.

The taste bud of the vallate papillae of the rat has been examined in the electron microscope by using the freeze-fracture technique. Tight junctions as a junctional complex are located at the taste pore, and form a seal between the oral environment and the taste buds. Tight junctions are not only within the taste buds, but also are demonstrated in the granular cell layers of the surrounding lingual epithelium. The present finding suggests that tight junctions of the taste pore link with those of the lingual epithelium. Desmosomes are observed in the buds, but they are smaller in size than in the surrounding lingual epithelium. Besides these junctions, within the buds, gap junctions containing particle-free zones are demonstrated which are called a subcompartment type.

Animals↗
PubMed1987

Morphological changes of intercellular junctions in the rat submandibular gland treated by long-term repeated administration of isoproterenol.

Long-term repeated administration of isoproterenol (IPR) 2 mg/100 g bw, once daily for ten days, resulted in morphological changes in the intercellular junctions of rat submandibular glands, which were investigated by means of the freeze-fracture technique. A significantly increased number of tight-junctional strands was present. These junctional strands extended much deeper toward the basal membrane than those in normal acinar cells. The basal frontier strands that branched from the networks of tight junctions were elongated and had either free-endings or terminal loops, which were more frequently observed in the IPR-treated acinar cells than in untreated acinar cells. Some of the strands of tight junctions were connected to small gap junctions. The diameters of gap junctions were not significantly different from those of control acinar cells. However, smooth areas devoid of particles were found intermingling with the usual packed particles in irregularly shaped small gap junctions. There was no significant difference between the desmosomes of IPR-treated and untreated acinar cells, in terms of either morphology or distribution. These changes in junctional morphology in the IPR-treated acinar cells resemble those seen in salivary glands during development, and in some experimental conditions including tumorous changes.

Animals↗
PubMed2004

Oncogenic Raf-1 regulates epithelial to mesenchymal transition via distinct signal transduction pathways in an immortalized mouse hepatic cell line.

The epithelial to mesenchymal transition (EMT) is considered to be an important event during malignant tumor progression and metastasis. Although Raf/MEK/ERK signaling causes EMT, the mechanisms, including the signaling pathways, are as yet unclear. In the present study we have examined the effects of signal transduction pathways on oncogenic Raf-1-induced EMT, using an immortalized mouse hepatic cell line. Oncogenic Raf-1-induced EMT is characterized by down-regulation of adherens and tight junctions and the reorganization of actin. An active Raf-1 gene was introduced into a mouse hepatic cell line which was then treated with the MAP kinase inhibitor PD98059, the p38 MAP kinase inhibitor SB203580, the PI3 kinase inhibitor LY294002 or the c-Src tyrosine kinase inhibitor PP2. The expression and localization of the adherens and tight junction proteins E-cadherin, occludin, ZO-1, claudin-1 and claudin-2 were determined by western blotting, RT-PCR and immunocytochemistry. The barrier function of tight junctions was assessed by measurements of transepithelial electric resistance (TER) and permeability in terms of fluxes of [(14)C]mannitol and [(14)C]inulin. In Raf-1-transfected cells expression of occludin and claudin-2 was markedly down-regulated at the protein and mRNA levels and the TER value was decreased, while the permeability was increased. The distribution of ZO-1, pancadherin and F-actin was changed from linear to zipper-like structures at cell borders. In Raf-1-transfected cells treated with PD98059 and SB203580, but not LY294002, expression and localization of claudin-2, but not occludin, recovered, together with barrier function, measured as the TER value. The distributions of ZO-1, pancadherin and F-actin also recovered on treatment with PD98059 and SB203580, but not LY294002. Expression and localization of occludin recovered slightly on treatment with PP2. Thus, oncogenic Raf-1 regulates EMT via distinct MAP kinase, p38 MAP kinase and c-Src tyrosine kinase signal pathways in the mouse hepatic cell line.

Actins↗
PubMed2002

Mechanisms of transjunctional transport of NaCl and water in proximal tubules of mammalian kidneys.

Tight junctions and the intercellular space of proximal tubules are not accessible to direct measurements of fluid composition and transport rates, but morphological and functional data permit analysis of diffusion and osmosis causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses through tight junctions along a chloride gradient, but against a sodium gradient. Calculation in terms of modified Nernst-Fick diffusion equation after eliminating electrical terms shows that transport rates (300-500 pmol min-1 mm-1 tubule length) and transepithelial voltage of +2 mV are in agreement with observations. Diffusion coefficients are Dtj=1500 microm2 s-1 in the S1 segment, and Dtj=90-100 microm2 s-1 in the S2 segment where apical intercellular NaCl concentration is 132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions with gap distance 6 A are impermeable to mannitol (effective molecular radius 4 A); reflection coefficients are sigma=0.92 for NaHCO3 and sigma=0.28 for NaCl, because of difference in anion size. The osmotic force is provided by a difference in effective transjunctional osmolality of 10 mOsm kg-1 in the S1 segment and 30 mOsm kg-1 in the S2 segment, where differences in transjunctional concentration contribute with 21 mOsm kg-1 for NaHCO3 and -4 mOsm kg-1 for NaCl. Transjunctional difference of 30 mOsm kg-1 causes a volume flow of 2 nL min-1 mm-1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow and diffusive and convective transport of NaCl. In conclusion, transjunctional diffusion and osmosis along gradients generated by transcellular transport of other solutes account for all NaCl transport in proximal tubules.

Animals↗
PubMed2006

Unconjugated bilirubin modulates the intestinal epithelial barrier function in a human-derived in vitro model.

Unconjugated bilirubin promotes intestinal secretion without affecting nutrient digestion or absorption. In the current study, the effects of unconjugated bilirubin (UCB) on the barrier function of the intestinal epithelium were investigated. The apical side of human intestinal cell line Caco-2 monolayers was challenged with purified UCB. Transepithelial electrical resistance and paracellular fluxes of 10 kD Cascade blue conjugate dextran were measured. Cell monolayer viability was studied using LDH release and trypan blue exclusion tests. Redistribution of enterocyte tight junction occludin was studied by confocal microscopy. Bilirubin induced a dose-dependent decrease of transepithelial electrical resistance (TEER). This effect was maximal at 6 h and tended to be reversed at 48 h. Oxidated bilirubin was ineffective. Bilirubin significantly increased fluorescent dextran paracellular passage. Cell viability was not affected by UCB over the 5-200 nmol/L concentration range. Finally, bilirubin triggered a reversible redistribution of tight junctional occludin. UCB increases the permeability of intestinal epithelium. This effect is reversible, dependent on the redox status of the molecule and the rearrangement of the tight junction. These data attribute to bilirubin a novel role of functional modulator of intestinal paracellular permeability in vitro.

Bilirubin↗
PubMed1997

Laminin reduces HSV-1 spread from cell to cell in human keratinocyte cultures.

Herpes simplex virus-1 (HSV-1) infects epidermal cells where it replicates and spreads from cell to cell. While some of the viral factors responsible for cell-to-cell spread are known, the host cell molecules and structures which are utilized by HSV-1 during spread are not well studied. Here we report that a laminin substrate reduced the ability of HSV-1 to spread from cell to cell in cultures of a human keratinocyte cell line (HaCaT). Laminin did not reduce spread of the virus by decreasing the viral replication rate. However, laminin did stimulate the formation of tight junctions between HaCaT cells, suggesting that tight junctions can affect cell-to-cell spread of HSV-1. Since laminin is an abundant component of the basement membrane in vivo, culturing cells on laminin may provide an assay which more accurately reflects the rate and mechanism of HSV-1 cell-to-cell spread in vivo.

Animals↗
PubMed1968

Morphological and functional aspects of an insect epidermal gland.

The sternal gland of primitive termites of the genus Zootermopsis (Z. nevadensis or Z. angusticollus) (Hagen) seems more organized than that of higher termites, in being comprised of three cell layers. It is also studded with about 200 campaniform sensilla. Below the meshwork cuticle of the gland lies a layer of columnar epithelial cells whose apical surfaces form a brush border, and whose basal surfaces are sculptured into a basketwork into which the second layer fits. Below the brush border are small microtubule-associated pits and coated vesicles. No channels can be seen either within or, except for the sensilla, between the cells. The second cell layer probably secretes the trail-following pheromone. Numerous electron-lucent droplets and large channels containing lipid micelles are found in the cytoplasm here, but the channels cannot be traced out of the secretory layer. The third layer consists of large pyriform cells. The campaniform sensilla are composed of three cells: the sensory cell proper whose dendrite carries a modified 9 + 0 sensory process, an accessory supporting cell that secretes an electron-opaque sheath, and an enveloping cell. At the cell borders of the sensillum, regions of septate and tight junction appear. There are also septate junctions between columnar cells and possibly tight junctions between columnar and secretory cells that would open an intracellular and molecular pathway to the endocuticle. The campaniform sensilla may be part of a feedback control system that determines the amount of pheromone deposited during trail laying.

Animals↗
PubMed1999

Transdifferentiation of NRP-152 rat prostatic basal epithelial cells toward a luminal phenotype: regulation by glucocorticoid, insulin-like growth factor-I and transforming growth factor-beta.

The role of basal epithelial cells in prostatic function, development and carcinogenesis is unknown. The ability of basal prostatic epithelial cells to acquire a luminal phenotype was explored in vitro using the NRP-152 rat dorsal-lateral prostate epithelial cell line as a model system. NRP-152, which was spontaneously immortalized and clonally derived, is an androgen-responsive and nontumorigenic cell line that has a basal cell phenotype under normal growth conditions. However, when placed in mitogen-deficient media, these cells undergo a dramatic morphological change to a luminal phenotype. Under these growth-restrictive conditions, immunocytochemical analysis shows that NRP-152 cells acquire the luminal markers Z0-1 (a tight-junction associated protein), occludin (integral tight-junction protein), and cytokeratin 18, and lose the basal markers cytokeratins 5 and 14. Total protein and mRNA levels of cytokeratins 8, 18, c-CAM 105 (the calcium-independent cell adhesion molecule) and Z0-1, as detected by western and/or northern blot analyses, respectively, are induced, while cytokeratin 5 and 15 are lost, and occludin is unchanged. Concomitant with this differentiation, expression of transforming growth factor-beta2 (TGF-beta2), TGF-beta3, and TGF-beta receptor type II (TbetaRII) is induced, while those of TGF-beta1 and TbetaRI remain essentially unchanged. Mitogens, such as insulin-like growth factor-I and dexamethasone inhibit luminal differentiation, while exogenous TGF-beta induces such differentiation. These data together with TGF-beta neutralization experiments using pan-specific antibody implicate an important role for autocrine TGF-beta in the induction of the luminal differentiation.

Animals↗
PubMed2002

Neutrophil transepithelial migration: evidence for sequential, contact-dependent signaling events and enhanced paracellular permeability independent of transjunctional migration.

Active migration of polymorphonuclear leukocytes (PMN) through the intestinal crypt epithelium is a hallmark of inflammatory bowel disease and correlates with patient symptoms. Previous in vitro studies have shown that PMN transepithelial migration results in increased epithelial permeability. In this study, we modeled PMN transepithelial migration across T84 monolayers and demonstrated that enhanced paracellular permeability to small solutes occurred in the absence of transepithelial migration but required both PMN contact with the epithelial cell basolateral membrane and a transepithelial chemotactic gradient. Early events that occurred before PMN entering the paracellular space included increased permeability to small solutes (<500 Da), enhanced phosphorylation of regulatory myosin L chain, and other as yet undefined proteins at the level of the tight junction. No redistribution or loss of tight junction proteins was detected in these monolayers. Late events, occurring during actual PMN transepithelial migration, included redistribution of epithelial serine-phosphorylated proteins from the cytoplasm to the nucleus in cells adjacent to migrating PMN. Changes in phosphorylation of multiple proteins were observed in whole cell lysates prepared from PMN-stimulated epithelial cells. We propose that regulation of PMN transepithelial migration is mediated, in part, by sequential signaling events between migrating PMN and the epithelium.

Actomyosin↗
PubMed1999

Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli.

Inflammatory mediators such as histamine and thrombin increase the tight-junction permeability of endothelial cells. Tight-junction permeability may be independently controlled, but is dependent on the adherens junction, where adhesion is achieved through homotypic interaction of cadherins, which in turn are associated with cytoplasmic proteins, the catenins. p120, also termed p120(cas)/p120(ctn), and its splice variant, p100, are catenins. p120, originally discovered as a substrate of the tyrosine kinase Src, is also a target for a protein kinase C-stimulated pathway in epithelial cells, causing its serine/threonine dephosphorylation. The present study shows that pharmacological activation of protein kinase C stimulated a similar pathway in endothelial cells. Activation of receptors for agents such as histamine (H1), thrombin and lysophosphatidic acid in the endothelial cells also caused serine/threonine dephosphorylation of p120 and p100, suggesting physiological relevance. However, protein kinase C inhibitors, although blocking the effect of pharmacological activation of protein kinase C, did not block the effects due to receptor activation. Calcium mobilization and the myosin-light-chain-kinase pathway do not participate in p120/p100 signalling. In conclusion, endothelial cells possess protein kinase C-dependent and -independent pathways regulating p120/p100 serine/threonine phosphorylation. These data describe a new connection between inflammatory agents, receptor-stimulated signalling and pathways potentially influencing intercellular adhesion in endothelial cells.

Calcium↗
PubMed1999

Hepatocyte growth factor/scatter factor decreases the expression of occludin and transendothelial resistance (TER) and increases paracellular permeability in human vascular endothelial cells.

Hepatocyte growth factor/scatter factor (HGF/SF), a multi function cytokine has been shown to regulate the expression of cell adhesion molecules in endothelial cells. In the current study, we examined the effects of HGF/SF on the function of tight junctions and the expression of occludin in these cells. Stimulation of human vascular endothelial cells with HGF/SF resulted in a concentration dependent increase in the paracellular permeability as measured using fluorescence labelled dextran but a decrease in the transendothelial cell resistance (TER) of the endothelial cells. Western blotting revealed that HGF/SF decreased the level of occludin in the cells, a primary tight junction forming protein. Immunofluorescence study indicated that shortly after treatment with HGF/SF there was a disturbance of the distribution of occludin and then a reduction in the staining of the molecule. It is concluded that HGF/SF decreases the expression of occludin, resulting in the functional change of tight junction.

Cell Line↗