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Results for “Tight junctions”

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At least 19 recordsLinked to original sources

PubMed1975

Retinal capillary junctions: ultrastructural tight junction artefacts induced by sodium ions and membrane reduction in streptozotocin diabetes.

Retinal capillary junctions were analysed in normal and diabetic rats and in a human retina with the electron microscope. Diabetes mellitus was induced with streptozotocin. The retinae were fixed in Palade's osmium tetroxide containing sodium or calcium ions and block-stained in uranyl acetate. With Ca-fixation, no significant difference in interendothelial cleft width was detected between retinal layers or between normal and diabetic retinae. Diabetes caused a narrowing of the clefts in the Na-fixed tissue X +/- SE, n=375; Normal: 78.6 +/- 300 A; Diabetic: 57.7 +/- 2.42 A; p less than 0.001). A significant correlation was found between cleft width and the length of the tight junctions or zonulae occludentes (p less than 0.001). In the nerve fibre layer of the Na-diabetic retina, where cleft narrowing was greatest, there was an increase in length of the zonulae occludentes from 22.8 +/- 2.2% to 41.6 +/- 3.7% (p less than 0.001). Ca-fixation prevented these changes, indicating that at least some zonulae occludentes were interendothelial extraction artefacts. In the normal retina, endothelial cell membrane thickness was greater with Ca- than Na-fixation (p less than 0.001). Diabetes caused a decrease in membrane thickness of Ca-fixed tissue (p less than 0.001). The diabetic decrease in membrane thickness may explain the increased fragility and increased permeability of diabetic capillaries. Calcium binding by endothelial cell membranes is of primary importance in anticoagulation which is defective in diabetes.

Animals↗

PubMed1979

The structure of tight junctions in human thyroid tumors. A systematic freeze-fracture study.

Tight junctions of normal human epithelium comprise 6--8 intramembranous ridges. Tight junctions of adenomas and one case of follicular carcinoma were morphologically identical with normal controls. Another follicular carcinoma (clinically less malignant than the case mentioned above), however, showed loss of junctional polarity with spreading of ridges on lateral cell membranes. One case of papillary carcinoma (clinically low malignancy) displayed only focal attenuations of the tight junction belt. Another more malignant tumor of the same histologic type showed breaks of ridges and focal interruptions of the tight junction meshwork. Cell membranes of two anaplastic carcinomas of high malignancy were completely devoid of tight junction ridges. We conclude that tight junction alterations are not necessarily implicated in malignant transformation and that they correspond with tumor differentiation rather than directly with a single parameter of thyroid tumor malignancy.

Adenocarcinoma↗

PubMed1978

An experimental analysis of interlamellar tight junctions in amphibian and mammalian C.N.S. myelin.

The distribution of interlamellar tight junctions was examined in myelin sheaths of Xenopus tadpole optic nerve and rabbit epiretinal tissue fixed with aldehydes, postfixed with osmium ferrocyanide and embedded in a water-soluble medium, Durcupan. Intramyelinic zonulae occludentes were clearly formed by fusion of adjacent intraperiod lines which corresponded to the external leaflets of oligodendrocytes. These occurred in register with other tight junctions present within successive lamellae and appeared as a series of radial lines extending either partially or totally across the thickness of the myelin sheath. This distribution of zonulae occludentes corresponded with that of tight junctional particle strands observed in freeze-fracture replicas. Analysis of intramyelinic vacuolation induced by hexachlorophene (HCP) intoxication indicated that lamellar splitting was frequently limited by the tight junctions. The intramyelinic zonulae occludentes also restricted the diffusion of colloidal lanthanum which had penetrated the myelin intraperiod gap following in vivo perineural injection. The results of this study provide evidence favouring a correspondence between interlamellar tight junctions and the 'radial component' of myelin described earlier by other investigators. Furthermore, observations of swollen myelin sheaths, resulting from HCP intoxication, suggest that these junctions may play a major role in maintaining myelin sheath integrity and limiting the extent of breakdown during certain pathological conditions.

Animals↗

PubMed1979

Tight junctions of dissociated and reaggregated embryonic lung cells.

Treatment of embryonic lung tissue with trypsin resulted in clustering of intramembrane particles (IMP) and gradual disassembly of tight junctions. In dissociated single cells kept in trypsin-free medium, IMP are randomly distributed but degradation of tight junctions continue. Vesicles containing tight junction elements were observed within the cytoplasm. It is therefore assumed that tight junctions may be degraded in two ways: breakdown of elements to IMP, and endocytosis. In cells reaggregated by rotation tight junctions reassembled only in hystotypic aggregates. Cycloheximide which interferes with histotypic reaggregation prevents the reassembly of tight junctions.

Animals↗

PubMed1979

Tight junction development between cultured hepatoma cells: possible stages in assembly and enhancement with dexamethasone.

Freeze-fracture and thin-section methods were used to study tight junction formation between confluent H4-II-E hepatoma cells that were plated in monolayer culture in media with and without dexamethasone, a synthetic glucocorticoid. Three presumptive stages in the genesis of tight junctions were suggested by these studies: 1) "formation zones" (smooth P-fracture face ridges deficient in intramembranous particles), apparently matched across a partially reduced extracellular space, develop between adjacent cells; 2) linear strands and aggregates of 9--11 nm particles collect along the ridges of the formation zones. The extracellular space was always reduced when these structures were found matched with pits in gentle E-face depressions; 3) the linear arrays of particles on the ridges associate within the membranes to form the fibrils characteristic of mature tight junctions. The formation zones resemble tight junctions in terms of size, complexity and the patterns of membrane ridges. Although some of the beaded particle specializations may actually be gap junctions, it is unlikely that all can be interpreted in this way. No other membrane structures were detected that could represent developmental stages of tight junctions. Dexamethasone (at 2 x 10(-6)M) apparently stimulated formation of tight junctions. Treated cultures had a greater number of formation zones and mature tight junctions, although no differences in qualitative features of the junctions were noted.

Animals↗

PubMed1979

Morphogenesis of tight junctions in the peritoneal mesothelium of the mouse embryo.

The peritoneal mesothelium of mouse embryos (12 to 18 day of gestation) was studied by freeze-fracture and in sections in order to reveal the initial formation of the tight junctions. Freeze-fracture observations showed three types of tight junctions. Type I consists of belt-like meshworks of elevations on the P face and of shallow grooves on the E face. No tight junctional particle can be seen either on the elevations or in the grooves. Type II shows rows of discontinuous particles on the elevations on the P face. Type III consists of strands forming ridges on the P face. On the E face, the grooves of Type II and III appear to be narrower and sharper than those of Type I. Quantitatively, Type I junctions are most numerous during the early stages (day 12-13) of embryonic development, while Type III junctions become more common in the later stages, and are the only type seen by day 18. Observations on sections, however, fail to distinguish between the three types. The results suggest that an initial sign of tight junction formation is close apposition of the two cell membranes in the junctional domain, without tight junctional particles. Later, the particles appear to be incorporated in the tight junctions and the strands form by fusion of the particles.

Animals↗

PubMed1979

Carbon tetrachloride induced proliferation of tight junctions in the rat liver as revealed by freeze-fracturing.

Application of carbon tetrachloride produced a progressive proliferation of tight junctions in the rat liver. This system proved to be rapid and highly reproducable and affords the opportunity for tracing the fate of tight junctions in freeze-fracture replicas, facilitating investigations on their formation and function. Beginning on day one carbon tetrachloride treatments resulted in the progressive loosening and fragmentation of the junctional meshwork. After three to four days the membrane outside the zonulae occludentes was extensively filled with proliferated discrete junctional elements often forming complex configurations. From the fifth day on the zonulae occludentes were restricted again predominantly around the bile canaliculus margins. But the junctional meshwork of the zonulae occludentes remained loosened in comparison to those in the control rats. It could be shown that tight junction proliferation on the lateral surface of the plasmalemma occurred both through de novo formation from discrete centers of growth by addition of intramembranous particles and through reorganization of preexistent junctional strands of the fragmented zonulae occludentes bodies. Whereas the large gap junctions close associated with the zonulae occludentes remained more or less unaffected during the experiments, small gap junctions increased in number after five days and were located at the margin or in the tight junction domain. It is assumed that the degeneration of the tight junctions served as a pool for intramembranous particles which form the gap junctions. The results of these observations are discussed in relation to those obtained in other systems.

Animals↗

PubMed1979

Degradation of tight junctions in HT29, a human colon adenocarcinoma cell line.

The process of tight junction degradation was followed in a cell line of human colon adenocarcinoma. Tight junctions are degraded by 2 mechanisms: (1) breakdown of junctional elements to intramembrane particles; (2) bleb formation by which tight-junctional elements are internalized into the cytoplasm or excluded into the medium. It is suggested that the first mechanism allows preservation of membrane particles for re-use, whereas the second is a mechanism by which the cells eliminate unneeded junctional elements.

Adenocarcinoma↗

PubMed1977

The effect of HCG on pinocytosis iwthin the canine inter-sertoli cell tight junction. A preliminary report.

The role of tight junctions in permeability barriers is now well established. Other roles for this junction have been postulated but have not been demonstrated. In both adult and prepubertal dogs, stimulation with human chorionic gonadotropin (hCG) results in an increased number of pinocytotic vesicles on the membrane faces enclosed by tight junctions within the inter-Sertoli cell junctions of the testis. It is suggested that these membranous regions, protected from the normal flow of intercellular fluids, may act as regions of selective intercellular exchange.

Animals↗

PubMed1975

Structure of tight junctions in epithelia with different permeability.

Freeze-fracture studies have shown a network of intramembrane fibrils in the tight junctions of epithelia. A direct correlation between the number of fibrils and junctional permeability has been suggested by previous studies. However, we have made two groups of observations showing that junctional permeability is not univocally related to the complexity of the network revealed by freeze-fracture. (i) The tight junctions of the rabbit ileum mucosa are permeable to lanthanum, although they have a complex network of fibrils resembling the junctions of toad urinary bladder, which are impermeable to lanthanum. (ii) The tight junctions of the toad urinary bladder are normally of low permeability; however, when the luminal solution is made hypertonic with lysine, junctional permeability markedly increases and lanthanum permeates through the tight junctions. In freeze-fracture replicas, no differences between the fibrils of control and lysine-treated bladders were found. Our results indicate that junctional permeability is controlled not only by the complexity of the fibrilar network, but that some features of the junctions or the fibrils themselves, not yet revealed by electron microscopy, play a central role in regulating epithelial permeability.

Animals↗

PubMed1977

Effect of protonated 2,4,6-triaminopyrimidine, a tight junction blocker, on intestinal transport in dog ileum in vivo.

Previous in vitro experiments suggest that protonated 2,4,6-triaminopyrimidine (TAP+) inhibits passive Na+ movement across tight junctions of various epithelial tissues. So far no evidence has been found that TAP+ interferes with other mucosal transport processes. Because blockage of the tight junctions would be a promising tool in studying intestinal transport physiology, the effect of TAP+ was investigated in the dog ileum in vivo. When TAP+ was added to a sodium-free mannitol solution, the transepithelial sodium diffusion potential was significantly decreased (60% inhibition with 34 mm TAP+); this would be expected if TAP+ inhibited NA+ permeation through tight junctions. However, TAP+ was also found to diminish Na+ and Cl- absorption. Furthermore, TAP+ increased unidirectional Na+ flux from plasma to lumen; this is opposite to the expected result of tight junction blockage. In addition, TAP+ reduced glucose, fructose, and xylose absorption by about 50%. In ileal loops exposed to cholera toxin, TAP+ enhanced secretion by a rate equal to the rate by which it reduced absorption in loops not exposed to cholera toxin. All changes induced by TAP+ approached normal within 4 hr of its removal from the perfusate. TAP+ did not cause nay mucosal damage that could be detected by protein leakage or by light microscopy. These studies show that TAP+ has many effects on intestinal transport processes that cannot be explained on the basis of tight junction blockage.

Animals↗

PubMed1979

Tight junctions adjacent to tumor stromal interface in human invasive transitional cell carcinomas.

Tight junctions adjacent to the tumor stromal interface in invading neoplastic cells of human urinary bladder carcinomas were observed. Basal lamina, collagen and elastic fibers, and cellular debris were found next to the tight junctions. An association between microenvironment (i.e., tumor necrosis) of the invading neoplastic cells and tight junction locations was suggested.

Carcinoma, Transitional Cell↗

PubMed1978

Morphological and functional changes in the tight junctions of the bile canaliculi induced by bile duct ligation.

Thin sections after bile duct ligation showed that the depth of tight junctions appeared to increase and that the distance between individual punctate contacts appeared to become irregular and wider than in controls. The freeze fracture replicas clearly demonstrated these changes in the tight junction morphology. Changes were noted most conspicuously in the tight junction three weeks after ligation. Measurements of the junctional morphology in control and ligated specimens showed that the junctional depth had increased two fold in the latter, whereas the number of strands had scarcely changed. Lanthanum tracer experiments showed that the tight junctions did not permit the passage of the tracer in normal nor ligated rats. It was concluded that the mechanism of obstructive jaundice could not be related to changes in junctional morphology causing increased junctional permeability.

Animals↗

PubMed1978

A freeze-fracture study of tight junctions in the pars convoluta and pars recta of the renal proximal tubule.

The morphology of tight junctions of the renal proximal tubule was studied comparing the pars convoluta and pars recta of rat, golden hamster, rabbit, cat, dog and tupaia. Though some interspecies variations were observed, the convoluted portions of the proximal tubules revealed quite uniformly very leaky tight junctions with mainly 1-2 strands. Along the whole proximal tubule of the rabbit kidney including the pars recta only minor differences of the zonulae occludentes were found. By contrast, the tight junctions of the pars recta in other species were much more elaborate, especially in cat and tupaia, having up to 6 strands and an overall depth of more than 150 nm. The implications of these findings are discussed with special regard to the functional differences between the pars convoluta and pars recta of the proximal tubule.

Animals↗

PubMed1979

Changes in tight junctions of rat intestinal crypt cells associated with changes in their mitotic activity.

The freeze-fracture appearance of tight junctions between rat duodenal crypt cells was studied in normal, mitotically suppressed, and mitotically enhanced animals. In normal animals crypt cell tight junctions present a pleomorphic appearance. The population includes junctions resembling postmitotic junctions of the intestinal villus, junctions composed largely or completely of particle chains, and regions at the cell apex in which junctions are absent for 3-4 micron distances laterally. Mitotic suppression by inhibition of DNA synthesis with cytosine arabinoside results in the disappearance of pleomorphism and crypt tight junctions progressively come to resemble those of the intestinal villus. With recovery from the drug and further synchronization with Colcemid, the crypt cells undergo a mitotic burst, and all varieties of unusual junctional configurations are observed with increased frequency.

Animals↗

PubMed1979

Gap and tight junctions in tunicates. Study in conventional and freeze-fracture techniques.

Intercellular junctions have been investigated in epidermis and pharyngeal epithelium of larvae and adults of various species of tunicates with conventional and freeze-fracture techniques. Gap and tight junctions were found, similar to those observed in vertebrate tissues. Gap junctions were frequent in glandular epithelia and in larval tissues. They were interpreted as ways of intercellular communication in these developing tissues. They were also particularly numerous in Phallusia pharyngeal cells. Tight junctions were found preferentially in adult pharyngeal and epidermal epithelia, where they were arranged in strands of distinct particles forming a belt-like network at the apical part of cells. These junctions were interpreted as providing a tight barrier between the internal medium and the external environment. In larvae, tight junctions were found only between epidermal cells of the tail. These junctions thus characterized completely differentiated tissues, where they might play, in tunicates and in vertebrates, the same role as septate junctions do in invertebrates.

Animals↗

PubMed2026

Phytolacca acinosa Roxb. induces intestinal toxicity through the histamine-MLCK-tight junction axis: Integrated evidence from proteomics, metabolomics, intestinal organoids and epithelial barrier validation.

Phytolacca acinosa Roxb. (PR) is a saponin-rich medicinal plant associated with gastrointestinal toxicity, but the mechanisms underlying PR-induced intestinal barrier injury remain unclear. In this study, raw PR extract was analytically characterized by UPLC-ZenoTOF-MS/MS, confirming triterpenoid saponins as the predominant constituents. C57BL/6 J mice were orally exposed to characterized PR extract (1.20 or 12.0 g/kg for 5 h), and Caco-2 cells and mouse intestinal organoids were used to assess epithelial toxicity and barrier disruption. Histopathology, ELISA, FITC-dextran permeability assays, immunofluorescence, CCK-8, LDH release, western blotting, DIA-based proteomics and untargeted metabolomics were integrated to define toxicological mechanisms. PR induced dose-dependent intestinal inflammation and barrier dysfunction, with the ileum as the most sensitive target. PR increased serum DAO and D-lactate and intestinal TNF-α and IL-1β, disrupted organoid morphology, enhanced epithelial permeability, and reduced ZO-1 expression. Proteomics revealed changes in inflammatory, lipid-metabolic, cytoskeletal and tight-junction pathways, including upregulation of MLCK3 and phospholipase-related proteins and downregulation of ZO-1 and ZO-2. Metabolomics identified histidine metabolism disturbance and histamine accumulation. Integrated multi-omics and pharmacological validation indicated that histamine activated the PLC/IP₃/Ca²⁺/CaM/MLCK cascade, promoting MLC phosphorylation, tight-junction disassembly and epithelial leakiness. MLCK inhibition partially restored ZO-1/ZO-2 expression and attenuated PR-induced epithelial injury. These findings identify the histamine-MLCK-tight junction axis as a key mechanism of PR-induced intestinal toxicity and support hazard identification of saponin-rich PR exposure.

Animals↗

PubMed1979

Tight junctions in the choroid plexus epithelium. A freeze-fracture study including complementary replicas.

The tight junctions of the choroid plexus epithelium of rats were studied by freeze-fracture. In glutaraldehyde-fixed material, the junctions exhibited rows of aligned particles and short bars on P-faces, the E-faces showing grooves bearing relatively many particles. A particulate nature of the junctional strands could be established by using unfixed material. The mean values of junctional strands from the lateral, third, and fourth ventricles of Lewis rats were 7.5 +/- 2.6, 7.4 +/- 2.2, and 7.5 +/- 2.4; and of Sprague-Dawley rats 7.7 +/- 3.4, 7.4 +/- 2.3, and 7.3 +/- 1.6. Examination of complementary replicas (of fixed tissue) showed that discomtinuities are present in the junctional strands: 42.2 +/- 4.6% of the length of measured P-face ridges were discontinuities, and the total amount of complementary particles in E-face grooves constituted 17.8 +/- 4.4% of the total length of the grooves, thus approximately 25% of the junctional strands can be considered to be discontinuous. The average width of the discontinuities, when corrected for complementary particles in E-face grooves, was 7.7 +/- 4.5 nm. In control experiments with a "tighter" tight junction (small intestine), complementary replicas revealed that the junctional fibrils are rather continuous and that the very few particles in E-face grooves mostly filled out discontinuities in the P-face ridges. Approximately 5% of the strands were found to be discontinuous. These data support the notion that the presence of pores in the junctional strands of the choroid plexus epithelium may explain the high transepithelial conductance in a "leaky" epithelium having a high number of junctional strands. However, loss of junctional material during fracturing is also considered as an alternative explanation of the present results.

Animals↗