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PubMed2002

A gene from the locus of enterocyte effacement that is required for enteropathogenic Escherichia coli to increase tight-junction permeability encodes a chaperone for EspF.

Disruption of the barrier properties of the enterocyte tight junction is believed to be important in the pathogenesis of diarrhea caused by enteropathogenic Escherichia coli (EPEC). This phenotype can be measured in vitro as the ability of EPEC to reduce transepithelial resistance (TER) across enterocyte monolayers and requires the products of the locus of enterocyte effacement (LEE) and, in particular, the type III secreted effector protein EspF. We report a second LEE-encoded gene that is also necessary for EPEC to fully reduce TER. rorf10 is not necessary for EPEC adherence, EspADB secretion, or formation of attaching and effacing lesions. However, rorf10 mutants have a diminished TER phenotype, reduced intracellular levels of EspF, and a reduced ability to translocate EspF into epithelial cells. The product of rorf10 is a 14-kDa intracellular protein rich in alpha-helices that specifically interacts with EspF but not with Tir or other EPEC secreted proteins. These properties are consistent with the hypothesis that rorf10 encodes a type III secretion chaperone for EspF, and we rename this protein CesF, the chaperone for EPEC secreted protein F.

Amino Acid Sequence↗
PubMed2000

Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin.

Occludin is an integral membrane protein of the epithelial cell tight junction (TJ). Its potential role in coordinating structural and functional events of TJ formation has been suggested recently. Using a rat salivary gland epithelial cell line (Pa-4) as a model system, we have demonstrated that occludin not only is a critical component of functional TJs but also controls the phenotypic changes associated with epithelium oncogenesis. Transfection of an oncogenic Raf-1 into Pa-4 cells resulted in a complete loss of TJ function and the acquisition of a stratified phenotype that lacked cell-cell contact growth control. The expression of occludin and claudin-1 was downregulated, and the distribution patterns of ZO-1 and E-cadherin were altered. Introduction of the human occludin gene into Raf-1-activated Pa-4 cells resulted in reacquisition of a monolayer phenotype and the formation of functionally intact TJs. In addition, the presence of exogenous occludin protein led to a recovery in claudin-1 protein level, relocation of the zonula occludens 1 protein (ZO-1) to the TJ, and redistribution of E-cadherin to the lateral membrane. Furthermore, the expression of occludin inhibited anchorage-independent growth of Raf-1-activated Pa-4 cells in soft agarose. Thus, occludin may act as a pivotal signaling molecule in oncogenic Raf- 1-induced disruption of TJs, and regulates phenotypic changes associated with epithelial cell transformation.

Animals↗
PubMed1997

Tight junction proteins form large complexes and associate with the cytoskeleton in an ATP depletion model for reversible junction assembly.

A key feature of the ischemic epithelial cell phenotype is the disruption of tight junctions (TJ). In a Manin-Darby canine kidney cell model for ischemia-reperfusion/hypoxia-reoxygenation injury which employs inhibitors of glycolysis (2-deoxy-D-glucose) and oxidative phosphorylation (antimycin A), transepithelial electrical resistance, a measure of TJ integrity, dropped rapidly, correlating well with declining ATP levels. Although immunocytochemical studies revealed only subtle changes in the distribution of the TJ proteins, zonula occludens (ZO)-1, ZO-2, and cingulin, examination of the Triton X-100 solubilities of these proteins, an indicator of cytoskeletal association, revealed a striking shift of all three TJ proteins into the insoluble pool, consistent with increased cytoskeletal interaction during ATP depletion. In addition, rate-zonal centrifugation analysis of a detergent-soluble fraction showed an increase in the amount of ZO-1 and ZO-2 in high density fractions following ATP depletion, providing further evidence for association of TJ proteins into a large complex possibly involving the cytoskeleton. Analysis of immunoprecipitation data from [35S]methionine-labeled cells revealed that ATP depletion led to the association of a 240-kDa protein with the ZO-1-containing complex. Western blots of this protein immunoprecipitated with anti-ZO-1 antibodies confirmed its identity as fodrin, a protein believed to link membrane and other proteins to the actin-based cytoskeleton. Together, our data suggest that in the absence of major immunocytochemical changes, ATP depletion leads TJ proteins to form large insoluble complexes and associate with the cytoskeleton. We propose a model in which a key, potentially regulated, step in the generation of the ischemic epithelial cell phenotype is the interaction between TJ proteins and fodrin and/or other cytoskeletal proteins.

Adenosine Triphosphate↗
PubMed1990

[Changes in lanthanum permeability of rat Sertoli cell tight junction after CDDP administration].

Using electron microscope, distribution of lanthanum tracer in the seminiferous epithelium was evaluated in adult male rats 2, 7, 25 and 53 days after single intraperitoneal injection of 3 mg/kg of CDDP. Lanthanum penetrated beyond the tight junction between Sertoli cells and the maximum penetration around the spermatid was found on the 7th day, when any degenerative changes of seminiferous epithelium were not recognized light microscopically. And 4 weeks pretreatment with Cephalantin and Kallikulein had no effects on this lanthanum tracer penetration around the spermatid. On decreasing this lanthanum tracer penetration after 7 days, some lanthanum was also found around the spermatocytes on the 53rd day but not around the spermatid. It is proposed that lanthanum tracer penetration beyond the Sertoli cell tight junction may be a morphological marker of early Sertoli cell dysfunction after CDDP administration.

Animals↗
PubMed1988

Modulation of tight junction formation in clone 4 MDCK cells by fatty acid supplementation.

Clone 4 MDCK cells, which generate a transepithelial electrical resistance (TER) of greater than 2,000 omega.cm2, were used to examine the role of membrane lipids in the barrier function of tight junctions. Phospholipid acyl groups were modified by supplementing cells grown in serum-free medium with 18:1(n-9), 18:3(n-3), or 18:3(n-6) complexed to albumin. Although both of these polyunsaturated fatty acids depress the melting point of membrane phospholipids, only 18:3(n-6) contributes significantly to eicosanoid production. Saturation indices of the phospholipids of cells supplemented with albumin alone, 18:1(n-9), 18:3(n-3), or 18:3(n-6) were 0.77, 0.78, 1.81, and 1.65, respectively. After trypsinization or removal of Ca2+, cells supplemented with 18:3(n-6) required longer periods of time to reestablish TER than did nonsupplemented cells or those incubated with 18:3(n-3) or 18:1(n-9). In contrast to MDCK strains I and II, clone 4 MDCK cells required continuous protein synthesis not only to reseal preexisting junctions after the addition of Ca2+ to Ca2+-depleted monolayers, but also to maintain steady-state TER. The rate of decay of TER in the presence of 1 microgram/ml of cycloheximide was 1.5 times greater in cells supplemented with either of the two 18:3 isomers than it was in nonsupplemented controls or in cells supplemented with 18:1(n-9). No significant difference was observed in the steady-state TER or selectivity of the tight junctions after fatty acid supplementation. These results suggest that there is a change in the dynamics of junction formation, rather than an alteration in their intrinsic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

An investigation of pulp capillaries and tight junctions between odontoblasts in cats.

The relative roles of capillaries and odontoblasts in the process of dentinogenesis and in pulp reactions to trauma and pathology are not clear. Contributing to the problem is the paucity of information on odontoblast--capillary relationships and tight junctions between odontoblasts. Using light microscopy the capillaries have now been examined in semithin transverse sections of perfusion fixed teeth at different positions in the long axis from the apical foramina to the pulp horns. Odontoblastic capillaries were prominent in the coronal and middle regions of canines and present at the same levels of incisors. In the pulp horns and just coronal to the pulp horns capillaries were all subodontoblastic but near the apex there were also a few odontoblastic capillary profiles. Transmission electron microscopy on ultrathin sections revealed that a high proportion of middle and coronal odontoblastic capillary profiles were fenestrated but subodontoblastic profiles coronal to the pulp horns were the most fenestrated. In a search for tight junctions in ultrathin sections some typical strands were observed between odontoblasts. The difficult of obtaining the latter evidence was explained by the cellular arrangement of the odontoblasts which differed markedly from an ideal parallel, apically coplanar arrangement. The results question the possibility that there is a direct exchange of materials between pulp capillaries and dentine in teeth of limited growth and provide a baseline for future experiments to test the permeability of the odontoblast layer.

Animals↗
PubMed2001

Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers.

Despite significant advances in the characterization of tight junction (TJ) proteins, little is known about how molecular changes relate to function due primarily to the limitations of conventional paracellular probes. To address this, the paracellular pathway in Caco-2 and T84 cell lines was profiled by measuring the permeabilities of 24 polyethylene glycols (PEG) of increasing molecular radius (3.5--7.4 A) analyzed by mass spectrometry. When combined with a paracellular sieving model, these data provided quantitative descriptors of the pathway under control conditions and after exposure to TJ modulators. PEG profiles in both cell lines conformed to a biphasic process involving a restrictive pore (radius 4.3--4.5 A) and a nonrestrictive component responsible for permeability of larger molecules. PEG profiling revealed significant differences between the effects of EGTA and sodium caprate (C10). The restrictive component of EGTA-treated cells lost all size discrimination due to an increase in pore radius. Sodium caprate had no effect on pore radius but increased permeability via a different mechanism possibly involving increased numbers of functional pores. PEG profiling provides a useful tool for probing the functional regulation of the paracellular route.

Biomarkers↗
PubMed2006

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.

Although dysregulation of tight junction (TJ) proteins is observed in epithelial malignancy, their participation in epithelial transformation is poorly understood. Recently we demonstrated that expression of oncogenic Raf 1 in Pa4 epithelial cells disrupts TJs and induces an oncogenic phenotype by downregulating expression of the TJ protein, occludin. Here we report the mechanism by which Raf 1 regulates occludin expression. Raf 1 inhibited occludin transcription by repressing a minimal segment of the occludin promoter in concert with upregulation of the transcriptional repressor, Slug without influencing the well-documented transcriptional repressor, Snail. Overexpression of Slug in Pa4 cells recapitulated the effect of Raf 1 on occludin expression, and depletion of Slug by small interfering RNA abrogated the effect of Raf 1 on occludin. Finally, chromatin immunoprecipitation assays and site-directed mutagenesis demonstrated a direct interaction between Slug and an E-box within the minimal Raf 1-responsive segment of the occludin promoter. These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition.

Animals↗
PubMed2002

Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice.

The tight junction (TJ) and its adhesion molecules, claudins, are responsible for the barrier function of simple epithelia, but TJs have not been thought to play an important role in the barrier function of mammalian stratified epithelia, including the epidermis. Here we generated claudin-1-deficient mice and found that the animals died within 1 d of birth with wrinkled skin. Dehydration assay and transepidermal water loss measurements revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal. These unexpected findings prompted us to reexamine TJs in the epidermis of wild-type mice. Close inspection by immunofluorescence microscopy with an antioccludin monoclonal antibody, a TJ-specific marker, identified continuous TJs in the stratum granulosum, where claudin-1 and -4 were concentrated. The occurrence of TJs was also confirmed by ultrathin section EM. In claudin-1-deficient mice, claudin-1 appeared to have simply been removed from these TJs, leaving occludin-positive (and also claudin-4-positive) TJs. Interestingly, in the wild-type epidermis these occludin-positive TJs efficiently prevented the diffusion of subcutaneously injected tracer (approximately 600 D) toward the skin surface, whereas in the claudin-1-deficient epidermis the tracer appeared to pass through these TJs. These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.

Animals↗
PubMedDate not supplied

Molecular complexity of vertebrate tight junctions (Review).

Separation of distinct body, organ and tissue compartments, and maintenance of epithelial cell polarity require tight junctions (TJ)-cell-cell junctions located in the apicolateral regions of epithelial and endothelial cells. Studies on the protein components of vertebrate TJ have revealed an intricate network of membrane, sub-membrane, cytoskeletal, and signalling molecules. How these molecules functionally interact to provide TJ with their functions, and what roles these molecules play in control of cell growth and differentiation is a fundamental problem in cell biology.

Animals↗
PubMed1992

Implications of a non-lamellar lipid phase for the tight junction stability. Part I: Influence of basic amino acids, pH and protamine on the bilayer-hexagonal II phase behaviour of PS-containing PE membranes.

Inverted lipid micelles have been proposed, among other biological functions, to constitute the structural basis of the so-called tight junctions, a special cell cell contact found in epithelia and endothelial, which act as a barrier for the paracellular solute passage. As a model system for the opening and closing of this gate, we investigated the formation of the inverted hexagonal phase (HII phase) in lipid bilayer systems consisting of egg phosphatidylethanolamine (egg PE) and mixed egg PE/bovine brain phosphatidylserine (BBPS) membranes. The formation of the HII phase was modulated by Ca2+ ions, pH, basic amino acids and protamine. The lamellar-HII phase transition temperature TH of pure egg PE membranes at pH 7.0 was lowered with increasing Ca2+ concentration. This effect was attenuated by the presence of 50 mM lysine methyl ester. In the mixed lipid system, this effect was also observed, but even more pronounced. However this effect could be compensated for by raising the Ca2+ concentration from 2 to 10 mM. This was not observed in the pure PE system. In the absence of Ca2+, lysine methyl ester and protamine lowered TH in both monocomponent and mixed lipid systems, whereas lysine caused the opposite effect. The pH-dependence of mixed lipid systems, which were investigated up to a BBPS content of 20 mol%, clearly shows that increasing PS content stabilizes the lamellar phase even at low pH. The results obtained with model membranes are discussed with respect to biological implications of the lamellar-HII phase transition for the modulation of tight junction stability.

Amino Acids↗
PubMed1990

Menadione increases hepatic tight-junctional permeability. Its effect can be decreased by butylated hydroxytoluene and verapamil.

Infusion of menadione at two different doses [2.7 mg and 5.5 mg in 100 microliters of dimethyl sulphoxide (DMSO)] into perfused rat livers for 30 min caused no or a 6-fold increase respectively in junctional permeability to horseradish peroxidase as compared with controls receiving 100 microliters of DMSO alone. The total glutathione (GSH) contents in these livers measured at the end of the experiments were 115% and 53%, compared with the controls. The free-radical scavenger butylated hydroxytoluene (BHT) (final concn. 5 microM) protected against the GSH depletion caused by the higher dose of menadione and partially decreased the menadione-induced increase in junctional permeability. Verapamil, a Ca2(+)-channel blocker which was added into the perfusion medium (final concn. 40 microM) 10 min before the infusion of 5.5 mg of menadione, completely abolished the effect of menadione on junctional permeability. Menadione exposure therefore increases tight-junctional permeability in the liver; this may involve a depletion of GSH and a subsequent increase in intracellular Ca2+.

Animals↗
PubMed1983

Increased tight junction permeability: a possible mechanism of oestrogen cholestasis.

Ethinyl oestradiol increased rat biliary permeability for 3H-inulin and 14C-sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment (P less than 0.0005) and bilirubin after 7 days (P less than 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol-treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein (P less than 0.0005 after 3 and 7 days), bromsulphthalein-glutathione conjugate (P less than 0.005 after 3 days; P less than 0.0005 after 7 days) and phenolphthalein glucuronide (P less than 0.005 after 3 days; P less than 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen-treated rats. 'Leakiness' of canalicular tight junctions may explain the pathophysiology of oestrogen-induced cholestasis.

Animals↗
PubMed1981

Epithelial solute permeability, ion transport and tight junction morphology in the developing lung of the fetal lamb.

1. Experiments were performed on exteriorized fetal lambs of between 69 days' gestation and term (147 days) in order to observe changes in lung volume and lung liquid secretion rate, and to delineate any alterations in solute permeability, ion transport and tight junction morphology in the maturing lung epithelium. Whilst it was technically possible to measure solute permeability as early as 69 days it was not feasible to apply the Ussing flux ratio technique before 84 days.2. Fetal lung liquid volume and secretion rate, when normalized for body weight, increase linearly with gestation, whereas tracheal volume expressed in the same manner remains constant.3. When expressed in terms of pore theory, epithelial permeability to small polar non-electrolytes does not change between 69 days and term (equivalent pore radius 0.66 nm and 0.64 nm respectively).4. In the immature fetus of 69-76 days, mean epithelial tight junction strand number is 8.3, whereas by the end of gestation it has fallen to 4.6.5. The transfer constants (min(-1)) for sodium and chloride movement in the direction lung liquid to plasma are, respectively, some 6 and 4 times greater at 84-87 days than at term.6. As in the mature fetus, the lung epithelium at 84-87 days actively transports chloride from plasma to lung lumen, albeit with a slightly reduced transport e.m.f. Sodium movement does not, at any gestational age, differ from the predictions for passive transfer.7. In lung liquid the concentrations of chloride and potassium increase and that of bicarbonate decreases during gestation, whilst that of sodium does not change. The rises in lung liquid chloride and potassium concentrations follow those in plasma, maintaining plasma/lung liquid ratios of 0.7 and 0.95 respectively. However, plasma bicarbonate remains constant and the plasma/lung liquid ratio for bicarbonate rises from 3 at 69-76 days to 20 near term as the lung liquid bicarbonate falls from 9.8 to under 2 m-mole kg(-1) H(2)O.8. Whereas lung liquid protein concentration remains constant and low at about 0.35 g l.(-1), plasma protein concentration rises from 23 g l.(-1) at 69-76 days to 43 g l.(-1) near term. During the same period arterial blood pressure doubles.

Animals↗
PubMed2006

Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability.

The effects of physiologically relevant increase in temperature (37-41 degrees C) on intestinal epithelial tight junction (TJ) barrier have not been previously studied. Additionally, the role of heat-shock proteins (HSPs) in the regulation of intestinal TJ barrier during heat stress remains unknown. Because heat-induced disturbance of intestinal TJ barrier could lead to endotoxemia and bacterial translocation during physiological thermal stress, the purpose of this study was to investigate the effects of modest, physiologically relevant increases in temperature (37-41 degrees C) on intestinal epithelial TJ barrier and to examine the protective role of HSPs on intestinal TJ barrier. Filter-grown Caco-2 intestinal epithelial cells were used as an in vitro intestinal epithelial model system to assess the effects of heat exposure on intestinal TJ barrier. Exposure of filter-grown Caco-2 monolayers to modest increases in temperatures (37-41 degrees C) resulted in a significant time- and temperature-dependent increases in Caco-2 TJ permeability. Exposure to modest heat (39 or 41 degrees C) resulted in rapid and sustained increases in HSP expression; and inhibition of HSP expression produced a marked increase in heat-induced increase in Caco-2 TJ permeability (P < 0.001). Heat exposure (41 degrees C) resulted in a compensatory increase in Caco-2 occludin protein expression and an increase in junctional localization. Inhibition of HSP expression prevented the compensatory upregulation of occludin protein expression and produced a marked disruption in junctional localization of occludin protein during heat stress. In conclusion, our findings demonstrate for the first time that a modest, physiologically relevant increase in temperature causes an increase in intestinal epithelial TJ permeability. Our data also show that HSPs play an important protective role in preventing the heat-induced disruption of intestinal TJ barrier and suggest that HSP mediated upregulation of occludin expression may be an important mechanism involved in the maintenance of intestinal epithelial TJ barrier function during heat stress.

Actins↗
PubMed1998

Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity.

Membrane-associated guanylate kinase homologs (MAGUKs) may play a role in cellular functions preventing tumorigenesis as indicated by the neoplastic phenotype caused by genetic loss of the MAGUK Dlg in Drosophila. To test this possibility, we examined the expression and subcellular localization of the tight junction MAGUK ZO-1, as well as the cell adhesion molecule E-cadherin, in paraffin-embedded breast cancer samples, using immunohistochemistry and confocal microscopy. As expected, normal tissue showed intense staining for ZO-1 at the position of the epithelial tight junctions, but this staining was reduced or lost in 69% of breast cancers analyzed (n = 48). In infiltrating ductal carcinomas (n = 38) there was a reduction in staining in 42% of well differentiated, in 83% of moderately differentiated and 93% of poorly differentiated tumors. ZO-1 staining was positively correlated with tumor differentiation (P = .011) and more specifically with the glandular differentiation of tumors (P = .0019). Reduction in ZO-1 staining was strongly correlated with reduced E-cadherin staining (P = 4.9 x 10(-5)). The results suggest that down-regulation of ZO-1 expression and its failure to accumulate at cell junctions may be causally related to cancer progression. To detect loss of heterozygosity, the ZO-1 gene tjp-1 was mapped relative to other markers in 15q13 and polymorphic markers flanking tjp-1 were identified. The marker D15S1019 showed loss of heterozygosity in 23% of informative tumors (n = 13). Loss of a tjp-1-linked marker suggests that genetic loss may, in some cases, be responsible for the reduction in ZO-1 expression in breast cancer.

Breast Neoplasms↗
PubMed2006

PPARgamma-regulated tight junction development during human urothelial cytodifferentiation.

Urothelial barrier function is maintained by apical membrane plaques and intercellular tight junctions (TJ). Little is known about the composition and regulation of TJ expression in human urothelium. In this study, we have characterised the expression of TJ components in situ and their regulation in an in vitro model of differentiating normal human urothelial (NHU) cells. In normal ureteric urothelium in situ, there was a differentiation-associated profile of claudins 3, 4, 5, 7, ZO1 and occludin proteins. Proliferating NHU cells in vitro expressed predominantly claudin 1 protein and transcripts for claudins 1-5 and 7. Following induction of differentiation by pharmacological activation of PPARgamma and blockade of EGFR, there was de novo expression of claudin 3 mRNA and protein and downregulation of claudin 2 transcription. There was also a massive increase in expression of claudin 4 and 5 proteins which was due to inhibition of proteasomal degradation of claudin 4 and consequential stabilisation of the claudin 5 heterodimerisation partner. NHU cell differentiation was accompanied by relocalisation of TJ proteins to intercellular junctions. The differentiation-associated development of TJ formation in vitro reflected the stage-related TJ expression seen in situ. This was distinct from changes in TJ composition of NHU cells mediated by increasing the calcium concentration of the medium. Our results imply a role for PPARgamma and EGFR signalling pathways in regulating TJ formation in NHU cells and support the hypothesis that TJ development is an integral part of the urothelial differentiation programme.

Anilides↗
PubMed2006

Dynamic changes in the cervical epithelial tight junction complex and differentiation occur during cervical ripening and parturition.

Cervical epithelia have numerous functions that include proliferation, differentiation, maintenance of fluid balance, protection from environmental hazards, and paracellular transport of solutes via tight junctions (TJs). Epithelial functions must be tightly regulated during pregnancy and parturition as the cervix undergoes extensive growth and remodeling. This study evaluated TJ proteins, as well as markers of epithelial cell differentiation in normal and cervical ripening defective mice to gain insights into how the permeability barrier is regulated during pregnancy and parturition. Although numerous TJ proteins are expressed in the nonpregnant cervix, claudins 1 and 2 are temporally regulated in pregnancy. Claudin 1 mRNA expression is increased, whereas claudin 2 expression declines. The cellular localization of claudin 1 shifts at the end of pregnancy (gestation d 18.75) to the plasma membrane in a lattice pattern, consistent with TJs in the apical cells. The timing of claudin 1-enriched TJs coincides with initiation of terminal differentiation of cervical squamous epithelia as evidenced by the increased expression of genes by differentiated epithelia late on gestation d 18. The cervical ripening defective steroid 5alpha-reductase type 1 deficient mouse, which has an elevated local progesterone concentration, also has aberrant claudin 1 and 2 expressions, fails to form claudin 1-enriched TJs, and lacks normal expression of genes involved in epithelial terminal differentiation. These data suggest that changes in permeability barrier properties during cervical ripening are, in part, negatively regulated by progesterone, and that dynamic changes in barrier properties of the cervix occur during pregnancy and parturition.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗