Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intercellular Junctions”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed2004

The gap junction protein connexin32 is a mouse lung tumor suppressor.

Although loss of connexin expression and/or gap junction intercellular communication correlates with decreased growth control and increased neoplastic potential, there is limited evidence directly linking gap junction intercellular communication function with tumor suppression in situ. Here, we show for the first time that a gap junction protein, connexin32 (Cx32), acts as a lung tumor suppressor in a mouse model. Cx32-deficient nontumorous lung tissue exhibited an increased proliferative index (P < 0.001), and, after exposure to the carcinogen diethylnitrosamine, Cx32-deficient mice exhibited a highly statistically significant (P < 0.001) increase in bronchioloalveolar lung tumor incidence (28 of 45, 62%) and a 45% increase in average multiplicity compared with wild-type mice (7 of 29, 24%). Tumors from Cx32-deficient mice also showed increased activation of mitogen-activated protein kinase (P < 0.001) compared with wild-type tumors, implicating this signaling pathway in Cx32/gap junction intercellular communication-associated lung tumorigenesis.

Animals↗
PubMed2002

Dupuytren's disease: physiologic changes in nodule and cord fibroblasts through aging in vitro.

The pathogenesis of the fibrotic disease Dupuytren's contracture remains unclear. The disease process includes two structurally distinct fibrotic elements, the nodule and the cord. It has been proposed that as the disease progresses, nodules develop into cords. To corroborate that hypothesis, the authors took advantage of cultured fibroblast differences found between gap junction intercellular communication and fibroblast-populated collagen lattice contraction. Paired fibroblast cell lines of nodules and cords derived from four patients with Dupuytren's disease were maintained in culture for at least eight passages. The presence of gap junction intercellular communication in nodule- and cord-derived fibroblasts was documented and reported as a coupling index. The contraction of free-floating nodule- or cord-derived collagen lattices was also documented and reported. Early passage (passage 4) cord-derived fibroblasts showed a significant increase in coupling index compared with passage 4 nodule-derived fibroblasts (4.0 +/- 0.4 versus 2.5 +/- 0.3, respectively), where p < or = 0.01. However, late passage (passage 8) nodule- and cord-derived fibroblasts were equivalent in their coupling index (4.1 +/- 0.4 versus 4.4 +/- 0.4, respectively). Early passage nodule-derived fibroblast-populated collagen lattices contracted by 64 percent, whereas late passage nodule-derived lattices showed less contraction, at only 40 percent. Early and late passage cord-derived lattices contracted 46 and 37 percent, respectively. All nodule- and cord-derived cell lines were statistically equivalent at lattice contraction by passage 8. These in vitro studies support the hypothesis that fibroblasts derived from Dupuytren's contracture nodules change their phenotype after undergoing repeated cell passage, acquiring a cord-like fibroblast phenotype. Dupuytren's nodules represent the early, active form of fibrosis in which cells are more proliferative, better at fibroblast-populated collagen lattice contraction, and display less gap junction intercellular communication. The speculation is that alterations in gap junction intercellular communication may be involved in the progression of Dupuytren's nodules to cords as the disease progresses.

Cell Communication↗
PubMed2004

Upregulation of the expression of tight and adherens junction-associated proteins during maturation of neonatal pancreatic islets in vitro.

Cell-cell contacts mediated by intercellular junctions are crucial for proper insulin secretion in the endocrine pancreas. The biochemical composition of the intercellular junctions in this organ and the role of junctional proteins in endocrine pancreatic dysfunctions are still unclear. In this study, we investigated the expression and cellular location of junctional and cytoskeletal proteins in cultured neonatal rat pancreatic islets. Neonatal B-cells had an impaired insulin secretion compared to adult cells. Cultured neonatal islets showed a time-dependent increase in the glucose-induced secretory response. The maturation of B-cells in vitro was accompanied by upregulation of the expression of some junctional proteins in islet cells. Neonatal islets cultured for only 24 h showed a low expression and a diffuse cytoplasmic location of the tight junctional proteins occludin and ZO-1 and of the adherens junctional proteins alpha- and beta-catenins, as demonstrated by immunoblotting and immunocytochemistry. Culturing islets for up to 8 days significantly increased the cell expression of these junctional proteins but not of the cytoskeletal proteins vinculin and alpha-actinin. A translocation of ZO-1 and catenins to the cell-cell contact region, as well as a higher association of F-actin with the intercellular junction, were also observed in neonatal islets following prolonged culturing. ZO-1 and beta-catenin were immunolocated in the endocrine pancreas of adult rats indicating that these junctional proteins are also expressed in this organ in situ. In conclusion, endocrine pancreatic cells express several junctional proteins that are upregulated following differentiation of the endocrine pancreas in vitro.

Adherens Junctions↗
PubMed2007

Endothelial cell motility is compatible with junctional integrity.

Confluent endothelial cells in culture are generally regarded as a model of resting endothelium in blood vessels (i.e., forming junctions at points of cell-cell contact, losing ability to proliferate in response to growth factors, and remaining stationary). However, incompatibility between junctional integrity and endothelial cell motility remains uncertain. The aim of this study was to determine whether endothelial cells (in colonies generated from differentiating embryonic stem cells in contact with OP9 stromal cell layer) have a resting endothelial phenotype (i.e., lack motility). Time-lapse analyses showed that though endothelial cells were connected to each other through adherens junctions and tight junctions, they were moving continuously within the colonies. Endothelial cell movement was accompanied by formation of lamellipodia, which transiently accumulated green fluorescent protein-tagged beta-actin and p41-Arc (a subunit of the actin-related protein 2/3 complex) at their anterior tips, suggesting that the movement is an active behavior of endothelial cells. Endothelial cell-specific expression of yellow fluorescent protein-tagged vascular endothelial-cadherin and claudin-5 revealed that adherens junctions and tight junctions persisted during endothelial cell migration. Furthermore, intercellular junctions underwent dynamic remodeling at the leading edge of moving endothelial cells. These results suggest that endothelial cells can remain highly motile without losing intercellular junctions.

Actin-Related Protein 2-3 Complex↗
PubMed2006

Gap junction-mediated intercellular communication between dendritic cells (DCs) is required for effective activation of DCs.

Gap junctions, formed by members of the connexin (Cx) family, are intercellular channels allowing direct exchange of signaling molecules. Gap junction-mediated intercellular communication (GJIC) is a widespread mechanism for homeostasis in organs. GJIC in the immune system is not yet fully understood. Although dendritic cells (DC) reportedly form cell-to-cell contact between DCs in nonlymphoid and lymphoid organs, GJIC between DCs remains unknown. In this study we examined whether DCs form GJIC. XS52 and bone marrow-derived DCs (BMDCs) were tested for GJIC by counting intercellular transfer of Lucifer Yellow microinjected into a cell. Either DC became effectively dye-coupled when activated with LPS plus IFN-gamma or TNF-alpha plus IFN-gamma. LPS- plus IFN-gamma-induced dye-coupling was mediated by DC-derived TNF-alpha. In addition, CpG plus IFN-gamma induced dye-coupling in BMDCs, which was also mediated by DC-derived TNF-alpha. LPS- plus IFN-gamma-induced activation of DCs (assessed by CD40 expression) was observed when there was cell-to-cell contact and was significantly blocked by heptanol, a gap junction blocker. These results indicate that cell-to-cell contact and GJIC are required for effective DC activation. In addition, heptanol significantly inhibited the LPS- plus IFN-gamma-induced up-regulation of the other costimulatory (i.e., CD80 and CD86) and MHC class II molecules expressed by BMDCs, and it significantly reduced their allostimulatory capacity. Among Cx members, Cx43 was up-regulated in dye-coupled BMDCs, and Cx mimetic peptide, a blocker of Cx-mediated GJIC, significantly inhibited the dye-coupling and activation, suggesting the involvement of Cx43. Thus, our study provides the first evidence for GJIC between DCs, which is required for effective DC activation.

Animals↗
PubMed1981

Fine structure of the fully keratinized hair cuticle in the head hair of the human.

The cuticle is composed of five cell layers in the cross section of the hair at a level of 100 mm above the scalp. Intercellular junctions between two cuticular cells are zonulae occludentes (tight junction); they consist of five layers. The gap junctions of the intercellular communications occur near the cortex. The trichohyalin granule appears in the cuticular cells of completely cornified head hair. The granule is generally smaller than that of the keratohyalin granule, and spherical in shape. The granule is not visible in the area near the surface of the hair. The keratin in the cytoplasm of the cuticular cell may originate from the trichohyalin granule.

Adult↗
PubMed1995

Studies on the tumor-promoting activities of additives in biomaterials: inhibition of metabolic cooperation by additives such as pigments and phenolic antioxidants.

The inhibitory activities on the intercellular gap-junctional communication were investigated using the V79 metabolic cooperation (MC) assay for the detection of tumor-promoting activities of additives such as pigments and phenolic antioxidants. Among six pigments, four chemicals showed inhibitory activities. The inhibitory potencies were ranked in the following order: sudan I > purple 201 > blue 204 > green 202. Sudan I and purple 201 showed stronger inhibitory activities than lithocholic acid, which is known to be a tumor promotor. However, quinizarine and red 225 did not inhibit at any concentration. Relating to eight phenolic antioxidants, four chemicals also showed inhibitory activities. Combining the present findings with previous ones, there are many factors that have tumor-promoting activities via inhibitory action on gap-junctional intercellular communication in biomaterials.

Animals↗
PubMed2001

PGE(2) is essential for gap junction-mediated intercellular communication between osteocyte-like MLO-Y4 cells in response to mechanical strain.

We have observed, in our previous studies, that fluid flow increases gap junction-mediated intercellular coupling and the expression of a gap junction protein, connexin 43, in osteocyte-like MLO-Y4 cells. Interestingly, this stimulation is further enhanced during the poststress period, indicating that a released factor(s) is likely to be involved. Here, we report that the conditioned medium obtained from the fluid flow-treated MLO-Y4 cells increased the number of functional gap junctions and connexin 43 protein. These changes are similar to those observed in MLO-Y4 cells directly exposed to fluid flow. Fluid flow was found to induce PGE(2) release and increase cyclooxygenase 2 expression. Treatment of the cells with PGE(2) had the same effect as fluid flow, suggesting that PGE(2) could be responsible for these autocrine effects. When PGE(2) was depleted from the fluid flow-conditioned medium, the stimulatory effect on gap junctions was partially, but significantly, decreased. Addition of the cyclooxygenase inhibitor, indomethacin, partially blocked the stimulatory effects of mechanical strain on gap junctions. Taken together, these studies suggest that the stimulatory effect of fluid flow on gap junctions is mediated, in part, by the release of PGE(2). Hence, PGE(2) is an essential mediator between mechanical strain and gap junctions in osteocyte-like cells.

Animals↗
PubMed2004

RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin.

Epithelial intercellular junctions regulate cell-cell contact and mucosal barrier function. Both tight junctions (TJs) and adherens junctions (AJs) are regulated in part by their affiliation with the F-actin cytoskeleton. The cytoskeleton in turn is influenced by Rho family small GTPases such as RhoA, Rac1, and Cdc42, all of which constitute eukaryotic targets for several pathogenic organisms. With a tetracycline-repressible system to achieve regulated expression in Madin-Darby canine kidney (MDCK) epithelial cells, we used dominant-negative (DN) and constitutively active (CA) forms of RhoA, Rac1, and Cdc42 as tools to evaluate the precise contribution of each GTPase to epithelial structure and barrier function. All mutant GTPases induced time-dependent disruptions in epithelial gate function and distinct morphological alterations in apical and basal F-actin pools. TJ proteins occludin, ZO-1, claudin-1, claudin-2, and junctional adhesion molecule (JAM)-1 were dramatically redistributed in the presence of CA RhoA or CA Cdc42, whereas only claudins-1 and -2 were redistributed in response to CA Rac1. DN Rac1 expression also induced selective redistribution of claudins-1 and -2 in addition to JAM-1, whereas DN Cdc42 influenced only claudin-2 and DN RhoA had no effect. AJ protein localization was unaffected by any mutant GTPase, but DN Rac1 induced a reduction in E-cadherin detergent solubility. All CA GTPases increased the detergent solubility of claudins-1 and -2, but CA RhoA alone reduced claudin-2 and ZO-1 partitioning to detergent-insoluble membrane rafts. We conclude that Rho family GTPases regulate epithelial intercellular junctions via distinct morphological and biochemical mechanisms and that perturbations in barrier function reflect any imbalance in active/resting GTPase levels rather than simply loss or gain of GTPase activity.

Actins↗
PubMedDate not supplied

[Effect of Ca ions and pH on the osmotic potential across the epithelium of the small intestine].

It was found that kinetic features of the behaviour of osmotic potential differences through epithelial cells layer were characteristic of determination of mechanic properties of separate structures of intercellular junctions. The quantitative estimation of the contribution of tight junction and simple junctions to the value of mechanic connection was performed. The mechanism of structure reorganisation in intercellular junctions under osmotic pressure are discussed. A model of intercellular junctions that accounts for the essential feature of transepithelial potential differences behavior under the osmotic pressure is proposed.

Animals↗
PubMed2002

Influence of tris(4-chlorophenyl)methanol (TCPM) on gap junction-mediated intercellular communication of cultured bovine granulosa cells.

Tris(4-chlorophenyl)methanol (TCPM) is a by-product in the manufacture of technical grade DDT, which is known to alter properties and functions of the female reproductive system. We investigated whether in vitro TCPM has an influence on the function of gap junction-mediated intercellular communication (GJIC) and gap junction protein expression of connexin 43 (Cx43) in cultured bovine granulosa cells. GJIC was assessed by fluorescent dye microinjection (dye-coupling). After a 1-h exposure to TCPM at a concentration of 32 microM, a significant (P<0.05) reduction in dye coupling occurred. The same result was obtained with o,p'-DDT. At a concentration of 32 microM both pesticides were cytotoxic as indicated by significant (P<0.05) increased propidium iodide staining of the cell nuclei. Little or no effect on the stainable pattern of connexons occurred after 1 h incubation time, while after 3 h treatment from 16 to 64 microM TCPM, a significant inhibition in the immunostaining resulted and the concentrations of 32 and 64 microM TCPM were cytotoxic for the granulosa cells. The freeze-fracture electron microscopy resulted in small differences in the morphology of gap junction plaques of cell cultures treated for 3 h with 8 or 16 microM TCPM in comparison to untreated cells. After treatment with 32 microM TCPM, gap junction plaques were very rarely detected and the lateral intramembraneous particles (IMP) distribution of many plasma membranes was strongly altered. Estimation of the cellular parameters may lead to an enhanced understanding of the mechanism of chemically induced toxicity by TCPM, that causes a general toxic effect on granulosa cells. We can conclude that TCPM is a toxic risk in the same manner as DDT.

Animals↗
PubMed2004

Cell-cell junctions between mammalian (human and rat) hepatic stellate cells.

To investigate intercellular junctions between mammalian hepatic stellate cells, we examined cultured human and rat hepatic stellate cells at the ultrastructural and molecular levels. Intercellular junctions between cultured human stellate cells, which developed irrespective of the type of culture substratum, were detected by transmission electron microscopy. On the basis of their characteristic ultrastructure, these junctions were identified in cultured human hepatic stellate cells as adherens junctions but not as tight junctions, desmosomes, or gap junctions. N-cadherin, alpha-catenin and beta-catenin, and p120ctn were detected by Western blotting in rat stellate cells as molecular components of the intercellular adhesive structures. Immunofluorescence for pan-cadherin, alpha-catenin, and beta-catenin were also detected in cultured human stellate cells. Moreover, pan-cadherin and beta-catenin were co-localized at the contact regions between the cultured human stellate cells. These data suggest that the junctional adhesion between the stellate cells can be formed both in vivo and in vitro. Thus, hepatic stellate cells may participate in the structural organization of the cells in liver lobules through the formation of intercellular adherens junctions. This is the first description of the presence of cell-cell junctions between hepatic stellate cells in mammals at the fine structural and molecular levels.

Animals↗
PubMed2003

Isoprenylcysteine carboxyl methyltransferase modulates endothelial monolayer permeability: involvement of RhoA carboxyl methylation.

RhoA and Rac1 regulate formation of stress fibers and intercellular junctions, thus modulating endothelial monolayer permeability. Posttranslational modifications of RhoA and Rac1 regulate enzyme activity and subcellular localization, resulting in altered cellular function. The role of RhoA and Rac1 carboxyl methylation in modulating endothelial monolayer permeability is not known. In this study, we found that inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT) with adenosine plus homocysteine or N-acetyl-S-geranylgeranyl-l-cysteine decreased RhoA carboxyl methylation, RhoA activity, and endothelial monolayer permeability, suggesting that RhoA carboxyl methylation may play a role in the ICMT-modulated monolayer permeability. Similar studies showed no effect of ICMT inhibition on Rac1 carboxyl methylation or localization. Bovine pulmonary artery endothelial cells (PAECs) stably overexpressing ICMT-GFP cDNA were established to determine if increased ICMT expression could alter RhoA or Rac1 carboxyl methylation, activation, and endothelial monolayer permeability. PAECs stably overexpressing ICMT demonstrated increased RhoA carboxyl methylation, membrane-bound RhoA, and RhoA activity. Additionally, PAECs stably overexpressing ICMT had diminished VE-cadherin and beta-catenin at intercellular junctions, with resultant intercellular gap formation, as well as enhanced monolayer permeability. These effects were blunted by adenosine plus homocysteine and by inhibition of RhoA, but not by inhibition of Rac1. These results indicate that ICMT modulates endothelial monolayer permeability by altering RhoA carboxyl methylation and activation, thus changing the organization of intercellular junctions. Therefore, carboxyl methylation of RhoA may modulate endothelial barrier function.

Adenosine↗
PubMed2005

Cyclic strain-mediated regulation of vascular endothelial occludin and ZO-1: influence on intercellular tight junction assembly and function.

OBJECTIVE: The vascular endothelium constitutes a highly effective fluid/solute barrier through the regulated apposition of intercellular tight junction complexes. Because endothelium-mediated functions and pathology are driven by hemodynamic forces (cyclic strain and shear stress), we hypothesized a dynamic regulatory link between endothelial tight junction assembly/function and hemodynamic stimuli. We, therefore, examined the effects of cyclic strain on the expression, modification, and function of 2 pivotal endothelial tight junction components, occludin and ZO-1. METHODS AND RESULTS: For these studies, bovine aortic endothelial cells were subjected to physiological levels of equibiaxial cyclic strain (5% strain, 60 cycles/min, 24 hours). In response to strain, both occludin and ZO-1 protein expression increased by 2.3+/-0.1-fold and 2.0+/-0.3-fold, respectively, concomitant with a strain-dependent increase in occludin (but not ZO-1) mRNA levels. These changes were accompanied by reduced occludin tyrosine phosphorylation (75.7+/-8%) and increased ZO-1 serine/threonine phosphorylation (51.7+/-9% and 82.7+/-25%, respectively), modifications that could be completely blocked with tyrosine phosphatase and protein kinase C inhibitors (dephostatin and rottlerin, respectively). In addition, there was a significant strain-dependent increase in endothelial occludin/ZO-1 association (2.0+/-0.1-fold) in parallel with increased localization of both occludin and ZO-1 to the cell-cell border. These events could be completely blocked by dephostatin and rottlerin, and they correlated with a strain-dependent reduction in transendothelial permeability to FITC-dextran. CONCLUSIONS: Overall, these findings indicate that cyclic strain modulates both the expression and phosphorylation state of occludin and ZO-1 in vascular endothelial cells, with putative consequences for endothelial tight junction assembly and barrier integrity.

Acetophenones↗
PubMed1993

Contractile activity and cell-cell contact regulate myofibrillar organization in cultured cardiac myocytes.

Adult feline ventricular myocytes cultured on a laminin-coated substratum reestablish intercellular junctions, yet disassemble their myofibrils. Immunofluorescence microscopy reveals that these non-beating heart cells lack vinculin-positive focal adhesions; moreover, intercellular junctions are also devoid of vinculin. When these quiescent myocytes are stimulated to contract with the beta-adrenergic agonist, isoproterenol, extensive vinculin-positive focal adhesions and intercellular junctions emerge. If solitary myocytes are stimulated to beat, an elaborate series of vinculin-positive focal adhesions develop which appear to parallel the reassembly of myofibrils. In cultures where neighboring myocytes reestablish cell-cell contact, myofibrils appear to reassemble from the fascia adherens rather than focal contacts. Activation of beating is accompanied by a significant reduction in the rate of total and cytoskeletal protein synthesis; in fact, myofibrillar reassembly, redevelopment of focal adhesions and fascia adherens junctions require no protein synthesis for at least 24 h, implying the existence of an assembly competent pool of cytoskeletal proteins. Maturation of the fasciae adherens and the appearance of vinculin within Z-line/costameres, does require de novo synthesis of new cytoskeletal proteins. Changes in cytoskeletal protein turnover appear dependent on beta agonist-induced cAMP production, but myofibrillar reassembly is a cAMP-independent event. Such observations suggest that mechanical forces, in the guise of contractile activity, regulate vinculin distribution and myofibrillar order in cultured adult feline heart cells.

Actins↗
PubMed1995

A study of intercellular relationships between trabecular bone and marrow stromal cells in the murine femoral metaphysis.

The cellular relationship between the substantia spongiosa of bone (cancellous or trabecular bone) and the haematopoietic bone marrow in the femoral metaphysis of C57BL/6NJCL mice was studied by transmission electron microscopy (TEM). Special attention was directed to intercellular junctions between osteocytes, osteoblasts, and bone marrow reticular cells. These were gap junctions and adhesive devices of simple architecture referred to as primitive junctions or zonula adherens-like junctions. Gap junctions were observed between osteocytes (within the trabeculae) and osteoblasts (at the trabecular surface) and between osteoblasts and marrow reticular cells. Gap junctions were also observed between the same cell type within each of these categories. These junctions involved the plasmalemmal membranes of adjacent cell bodies and of processes. Primitive cell junctions had a similar cellular distribution. Quantitative analysis of the cell types covering or positioned around the trabecular bones and of gap junctions between these and other cells was carried out by TEM. It was found that osteoblasts were the most numerous cell type, occupying 31% of the total of each cell type positively identified around the trabeculae (31%), while pre-osteoblasts, (flattened bone marrow reticular cells) took up 26%. These data emphasise the intimate relationship of the various mesenchymal cells based on processes and intercellular junctions, and point to an anatomical and probably functional integration of trabeculae and marrow. The functional significance and putative regulatory activity of this unit are discussed.

Animals↗
PubMed1971

Coexistence of gap and sseptate junctions in an invertebrate epithelium.

The intercellular junctions of the epithelium lining the hepatic caecum of Daphnia were examined. Electron microscope investigations involved both conventionally fixed material and tissue exposed to a lanthanum tracer of the extracellular space. Both septate junctions and gap junctions occur between the cells studied. The septate junctions lie apically and resemble those commonly discerned between cells of other invertebrates. They are atypical in that the high electron opacity of the extracellular space obscures septa in routine preparations. The gap junctions are characterized by a uniform 30 A space between apposed cell membranes. Lanthanum treatment of gap junctions reveals an array of particles of 95 A diameter and 120 A separation lying in the plane of the junction. As this pattern closely resembles that described previously in vertebrates, it appears that the gap junction is phylogenetically widespread. In view of evidence that the gap junction mediates intercellular electrotonic coupling, the assignment of a coupling role to other junctions, notably the septate junction, must be questioned wherever these junctions coexist.

Animals↗