Sepsis and mechanical ventilation alter the tight junction proteins in rat lungs in vivo

This study aimed to assess the effect of gonadotrophin suppression and FSH replacement on testicular tight junction dynamics and blood–testis barrier (BTB) organisation in vivo, utilising the seasonal breeding Djungarian hamster. Confocal immunohistology was used to assess the cellular organisation of tight junction proteins and real-time PCR to quantify tight junction mRNA. The effect of tight junction protein organisation on the BTB permeability was also investigated using a biotin-linked tracer. Tight junction protein (claudin-3, junctional adhesion molecule (JAM)-A and occludin) localisation was present but disorganised after gonadotrophin suppression, while mRNA levels (claudin-11, claudin-3 and occludin) were significantly (two- to threefold) increased. By contrast, both protein localisation and mRNA levels for the adaptor protein zona occludens-1 decreased after gonadotrophin suppression. FSH replacement induced a rapid reorganisation of tight junction protein localisation. The functionality of the BTB (as inferred by biotin tracer permeation) was found to be strongly associated with the organisation and localisation of claudin-11. Surprisingly, JAM-A was also recognised on spermatogonia, suggesting an additional novel role for this protein in trans-epithelial migration of germ cells across the BTB. It is concluded that gonadotrophin regulation of tight junction proteins forming the BTB occurs primarily at the level of protein organisation and not gene transcription in this species, and that immunolocalisation of the organised tight junction protein claudin-11 correlates with BTB functionality.

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Allyl Isothiocyanate Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mouse by Enhancing Tight Junction and Mucin Expression

International Journal of Molecular Sciences ◽

10.3390/ijms19072025 ◽

2018 ◽

Vol 19 (7) ◽

pp. 2025 ◽

Cited By ~ 5

Author(s):

Min Kim ◽

Seungho Choi ◽

Sun Kim ◽

Yeo Yoon ◽

Ju-Hee Kang ◽

...

Keyword(s):

Tight Junction ◽

Cell Line ◽

Allyl Isothiocyanate ◽

In Vivo Studies ◽

Intestinal Barrier Function ◽

Tight Junction Proteins ◽

Mucin Expression ◽

Junction Proteins

Inflammatory bowel disease (IBD) is characterized by chronic or recurrent inflammation of the gastrointestinal tract. Even though the current strategies to treat IBD include anti-inflammatory drugs and immune modulators, these treatments have side-effects. New strategies are, therefore, required to overcome the limitations of the therapies. In this study, we investigated the anti-colitic effects of allyl isothiocyanate (AITC), which is an active ingredient present in Wasabia japonica. The DSS-induced colitis model in the mouse was used to mimic human IBD and we observed that AITC treatment ameliorated the severity of colitis. We further studied the mechanism involved to ameliorate the colitis. To investigate the involvement of AITC on the intestinal barrier function, the effect on the intercellular tight junction was evaluated in the Caco-2 cell line while mucin expression was assessed in the LS174T cell line. AITC positively regulated tight junction proteins and mucin 2 (MUC2) against DSS-induced damage or depletion. Our data of in vivo studies were also consistent with the in vitro results. Furthermore, we observed that MUC2 increased by AITC is dependent on ERK signaling. In conclusion, we propose that AITC can be considered as a new strategy for treating IBD by modulating tight junction proteins and mucin.

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Redistribution of Tight Junction Proteins During EPEC Infection In Vivo

Inflammation ◽

10.1007/s10753-010-9285-1 ◽

2010 ◽

Vol 35 (1) ◽

pp. 23-32 ◽

Cited By ~ 20

Author(s):

Qiang Zhang ◽

Qiurong Li ◽

Chenyang Wang ◽

Ning Li ◽

Jieshou Li

Keyword(s):

Tight Junction ◽

Tight Junction Proteins ◽

Junction Proteins

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Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated withCitrobacter rodentium-induced colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90551.2008 ◽

2009 ◽

Vol 297 (4) ◽

pp. G735-G750 ◽

Cited By ~ 46

Author(s):

V. S. Conlin ◽

X. Wu ◽

C. Nguyen ◽

C. Dai ◽

B. A. Vallance ◽

...

Keyword(s):

Tight Junction ◽

Myosin Light Chain ◽

Intestinal Barrier ◽

Paracellular Permeability ◽

Epithelial Barrier ◽

Tight Junction Proteins ◽

Epithelial Barrier Function ◽

Junction Proteins

Attaching and effacing bacterial pathogens attach to the apical surface of epithelial cells and disrupt epithelial barrier function, increasing permeability and allowing luminal contents access to the underlying milieu. Previous in vitro studies demonstrated that the neuropeptide vasoactive intestinal peptide (VIP) regulates epithelial paracellular permeability, and the high concentrations and close proximity of VIP-containing nerve fibers to intestinal epithelial cells would support such a function in vivo. The aim of this study was to examine whether VIP treatment modulated Citrobacter rodentium-induced disruption of intestinal barrier integrity and to identify potential mechanisms of action. Administration of VIP had no effect on bacterial attachment although histopathological scoring demonstrated a VIP-induced amelioration of colitis-induced epithelial damage compared with controls. VIP treatment prevented the infection-induced increase in mannitol flux a measure of paracellular permeability, resulting in levels similar to control mice, and immunohistochemical studies demonstrated that VIP prevented the translocation of tight junction proteins: zonula occludens-1, occludin, and claudin-3. Enteropathogenic Escherichia coli (EPEC) infection of Caco-2 monolayers confirmed a protective role for VIP on epithelial barrier function. VIP prevented EPEC-induced increase in long myosin light chain kinase (MLCK) expression and myosin light chain phosphorylation (p-MLC). Furthermore, MLCK inhibition significantly attenuated bacterial-induced epithelial damage both in vivo and in vitro. In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation.

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Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle1

Journal of Animal Science ◽

10.2527/jas.2016.0892 ◽

2017 ◽

Vol 95 (3) ◽

pp. 1313-1324 ◽

Cited By ~ 1

Author(s):

L. Zhang ◽

L. F. Schütz ◽

C. L. Robinson ◽

M. L. Totty ◽

L. J. Spicer

Keyword(s):

Gene Expression ◽

Tight Junction ◽

Tight Junction Proteins ◽

Junction Proteins

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Epithelial differentiation and intercellular junction formation in the mouse early embryo

Development ◽

10.1242/dev.116.supplement.105 ◽

1992 ◽

Vol 116 (Supplement) ◽

pp. 105-112

Author(s):

Tom P. Fleming ◽

Qamar Javed ◽

Mark Hay

Keyword(s):

Tight Junction ◽

Intercellular Junctions ◽

Early Embryo ◽

Control Mechanisms ◽

Tight Junction Proteins ◽

Cell Stage ◽

Tight Junction Formation ◽

Junction Formation ◽

Junction Proteins

Trophectoderm differentiation during blastocyst formation provides a model for investigating how an epithelium develops in vivo. This paper briefly reviews our current understanding of the stages of differentiation and possible control mechanisms. The maturation of structural intercellular junctions is considered in more detail. Tight junction formation, essential for blastocoele cavitation and vectorial transport activity, begins at compaction (8-cell stage) and appears complete before fluid accumulation begins a day later (approx 32-cell stage). During this period, initial focal junction sites gradually extend laterally to become zonular and acquire the peripheral tight junction proteins ZO-1 and cingulin. Our studies indicate that junction components assemble in a temporal sequence with ZO-1 assembly preceding that of cingulin, suggesting that the junction forms progressively and in the ‘membrane to cytoplasm’ direction. The protein expression characteristics of ZO-1 and cingulin support this model. In contrast to ZO-1, cingulin expression is also detectable during oogenesis where the protein is localised in the cytocortex and in adjacent cumulus cells. However, maternal cingulin is metabolically unstable and does not appear to contribute to later tight junction formation in trophectoderm. Cell-cell interactions are important regulators of the level of synthesis and state of assembly of tight junction proteins, and also control the tissue-specificity of expression. In contrast to the progressive nature of tight junction formation, nascent desmosomes (formed from cavitation) appear mature in terms of their substructure and composition. The rapidity of desmosome assembly appears to be controlled by the time of expression of their transmembrane glycoprotein constitutents; this occurs later than the expression of more cytoplasmic desmosome components and intermediate filaments which would therefore be available for assembly to occur to completion.

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Tight Junction Proteins Claudin-2 and -12 Are Critical for Vitamin D-dependent Ca2+ Absorption between Enterocytes

Molecular Biology of the Cell ◽

10.1091/mbc.e07-09-0973 ◽

2008 ◽

Vol 19 (5) ◽

pp. 1912-1921 ◽

Cited By ~ 269

Author(s):

Hiroki Fujita ◽

Kotaro Sugimoto ◽

Shuichiro Inatomi ◽

Toshihiro Maeda ◽

Makoto Osanai ◽

...

Keyword(s):

Vitamin D ◽

Tight Junction ◽

Active Form ◽

Intestinal Epithelial ◽

Tight Junction Proteins ◽

Dihydroxyvitamin D ◽

Intestinal Epithelia ◽

Junction Proteins

Ca2+ is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is known to promote intestinal Ca2+ absorption. However, the molecules driving the paracellular Ca2+ absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca2+ transport and that expression of these claudins could be induced by 1α,25(OH)2D3. Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca2+ absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1α,25(OH)2D3 through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca2+ channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.

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Colon epithelial cell TGFβ signaling modulates the expression of tight junction proteins and barrier function in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00053.2021 ◽

2021 ◽

Cited By ~ 1

Author(s):

Paula Marincola Smith ◽

Yash A Choksi ◽

Nicholas O Markham ◽

David N Hanna ◽

Jinghuan Zi ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Tight Junction ◽

Barrier Function ◽

Protein Translation ◽

Tight Junction Proteins ◽

Tgfβ Signaling ◽

Mouse Colon ◽

Junction Proteins

Background: Defective barrier function is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). While TGFβ signaling defects have been associated with IBD and CAC, few studies have examined the relationship between TGFβ and intestinal barrier function. Here, we examine the role of TGFβ signaling via SMAD4 in modulation of colon barrier function. Methods: The Smad4 gene was conditionally deleted in the intestines of adult mice and intestinal permeability assessed using an in vivo 4kD FITC-Dextran (FD4) permeability assay. Mouse colon was isolated for gene expression (RNA-sequencing), western blot, and immunofluorescence analysis. In vitro colon organoid culture was utilized to assess junction-related gene expression by qPCR and trans-epithelial resistance (TER). In silico analyses of human IBD and colon cancer databases were performed. Results: Mice lacking intestinal expression of Smad4 demonstrate increased colonic permeability to FD4 without gross mucosal damage. mRNA/protein expression analyses demonstrate significant increases in Cldn2/Claudin 2 and Cldn8/Claudin 8, and decreases in Cldn3, Cldn4, and Cldn7/Claudin 7 with intestinal SMAD4 loss in vivo without changes in Claudin protein localization. TGFb1/BMP2 treatment of polarized SMAD4+ colonoids increases TER. Cldn2, Cldn4, Cldn7, and Cldn8 are regulated by canonical TGFβ signaling, and TGFβ-dependent regulation of these genes is dependent on nascent RNA transcription (Cldn2, Cldn4, Cldn8) but not nascent protein translation (Cldn4, Cldn8). Human IBD/colon cancer specimens demonstrate decreased SMAD4, CLDN4, CLDN7, and CLDN8 and increased CLDN2 compared to healthy controls. Conclusion: Canonical TGFβ signaling modulates the expression of tight junction proteins and barrier function in mouse colon.

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