Maturation of tight junctions in guinea-pig cecal epithelium

Mora-Galindo, J

doi:10.1007/bf00219014

Cited by 13 publications

(5 citation statements)

References 31 publications

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“…This is particularly evident in intestinal crypt cells and in mitotic cells (Tice et al. , 1979; Mora-Galindo, 1986), although also readily found in freeze-fracture images of tight junctions in Madin–Darby canine kidney (MDCK) cells (e.g., Figure 1, arrows) and in other epithelial cells and tissues. In addition, a cldn-binding domain of an intestinal toxin resulted in disaggregation of cldn strands preferentially from the basalmost strands, suggesting that these were more dynamic or unstable and thus more accessible than apical strands (Sonoda et al.…”

Section: Introductionmentioning

confidence: 82%

Newly synthesized claudins but not occludin are added to the basal side of the tight junction

Itallie

Lidman

Tietgens

et al. 2019

MBoC

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A network of claudin strands creates continuous cell–cell contacts to form the intercellular tight junction barrier; a second protein, occludin, is associated along these strands. The physiological barrier remains stable despite protein turnover, which involves removal and replacement of claudins both in the steady state and during junction remodeling. Here we use a pulse–block–pulse labeling protocol with fluorescent ligands to label SNAP/CLIP-tags fused to claudins and occludin to identify their spatial trafficking pathways and kinetics in Madin–Darby canine kidney monolayers. We find that claudins are first delivered to the lateral membrane and, over time, enter the junction strand network from the basal side; this is followed by slow replacement of older claudins in the strands. In contrast, even at early times, newly synthesized occludin is found throughout the network. Taking the results together with our previous documentation of the mechanism for claudin strand assembly in a fibroblast model, we speculate that newly synthesized claudins are added at strand breaks and free ends; these are most common in the basalmost edge of the junction. In contrast, occludin can be added directly within the strand network. We further demonstrate that claudin trafficking and half-life depend on carboxy-terminal sequences and that different claudins compete for tight junction localization.

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Section: Introductionmentioning

confidence: 82%

Newly synthesized claudins but not occludin are added to the basal side of the tight junction

Itallie

Lidman

Tietgens

et al. 2019

MBoC

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“…17,49–51 Interestingly, crypt, but not surface, epithelial express claudin-2, consistent with the greater paracellular permeability of the former. 52–54 …”

Section: Pathophysiologic Regulation Of Leak and Pore Pathwaysmentioning

confidence: 99%

“…Given the greater paracellular permeability of crypt, relative to surface, epithelium, it is notable that crypt epithelia have significant intracellular occludin pools, while surface epithelia, do not. 52–54 …”

Section: Pathophysiologic Regulation Of Leak and Pore Pathwaysmentioning

confidence: 99%

“…Together, this results in a skewing of the crypt:villus surface area ratio. Because the leak pathway of crypt tight junctions is far more permeable than in the villus 52–54 , this likely increases leak pathway flux. However, pore pathway flux may be reduced as a result of the overall loss of surface area.…”

Section: Association Of Intestinal Barrier Function With Intestinal Dmentioning

confidence: 99%

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The intestinal epithelial barrier: a therapeutic target?

Odenwald

Turner

2016

Nat Rev Gastroenterol Hepatol

918

670

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A fundamental function of the intestinal epithelium is to act as a barrier that regulates interactions between the luminal contents, such as the intestinal microbiota, the underlying immune system, and the remainder of the body, while supporting vectorial transport of nutrients, water, and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic. Unfortunately, most current clinical data are correlative, making it difficult to separate cause from effect in interpreting significance of barrier loss. Some data from experimental animal models suggest that compromised epithelial integrity may play a pathogenic role in specific gastrointestinal diseases, but no FDA-approved therapies for targeting the epithelial barrier are presently available. In order for this goal to be achieved, a deeper understanding of both disease pathogenesis and mechanisms of barrier regulation must be reached.

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“…We speculated that the well-known actions of Snail in epithelial cell differentiation might offer a mechanistic connection for this barrier defect. In vivo, intestinal and colonic epithelial cells are constantly entering a state of differentiation from precursor crypt cells (20), and tight junctions tend to mature as cells progress from less to more mature (44). Colorectal cancer cell lines are, to varying degrees, committed to a particular linage, such as absorptive or mucus secreting, depending on their derivation and adaptation.…”

Section: Discussionmentioning

confidence: 99%

Slug and Snail have differential effects in directing colonic epithelial wound healing and partially mediate the restitutive effects of butyrate

Swain

Grifka-Walk

Gripentrog

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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Restitution of wounds in colonic epithelium is essential in the maintenance of health. Microbial products, such as the short-chain fatty acid butyrate, can have positive effects on wound healing. We used an in vitro model of T84 colonic epithelial cells to determine if the Snail genes Slug ( SNAI2) and Snail ( SNAI1), implemented in keratinocyte monolayer healing, are involved in butyrate-enhanced colonic epithelial wound healing. Using shRNA-mediated Slug/Snail knockdown, we found that knockdown of Slug (Slug-KD), but not Snail (Snail-KD), impairs wound healing in scratch assays with and without butyrate. Slug and Snail had differential effects on T84 monolayer barrier integrity, measured by transepithelial resistance, as Snail-KD impaired the barrier (with or without butyrate), whereas Slug-KD enhanced the barrier, again with or without butyrate. Targeted transcriptional analysis demonstrated differential expression of several tight junction genes, as well as focal adhesion genes. This included altered regulation of Annexin A2 and ITGB1 in Slug-KD, which was reflected in confocal microscopy, showing increased accumulation of B1-integrin protein in Slug-KD cells, which was previously shown to impair wound healing. Transcriptional analysis also indicated altered expression of genes associated with epithelial terminal differentiation, such that Slug-KD cells skewed toward overexpression of secretory cell pathway-associated genes. This included trefoil factors TFF1 and TFF3, which were expressed at lower than control levels in Snail-KD cells. Since TFFs can enhance the barrier in epithelial cells, this points to a potential mechanism of differential modulation by Snail genes. Although Snail genes are crucial in epithelial wound restitution, butyrate responses are mediated by other pathways as well. NEW & NOTEWORTHY Although butyrate can promote colonic mucosal healing, not all of its downstream pathways are understood. We show that the Snail genes Snail and Slug are mediators of butyrate responses. Furthermore, these genes, and Slug in particular, are necessary for efficient restitution of wounds and barriers in T84 epithelial cells even in the absence of butyrate. These effects are achieved in part through effects on regulation of β1 integrin and cellular differentiation state.

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Maturation of tight junctions in guinea-pig cecal epithelium

Cited by 13 publications

References 31 publications

Newly synthesized claudins but not occludin are added to the basal side of the tight junction

Newly synthesized claudins but not occludin are added to the basal side of the tight junction

The intestinal epithelial barrier: a therapeutic target?

Slug and Snail have differential effects in directing colonic epithelial wound healing and partially mediate the restitutive effects of butyrate

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