Altered expression of tight junction proteins and matrix metalloproteinases in thiamine-deficient mouse brain

Beauchesne, Élizabeth; Desjardins, Paul; Hazell, Alan S.; Butterworth, Roger F.

doi:10.1016/j.neuint.2009.03.014

Cited by 26 publications

(16 citation statements)

References 28 publications

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“…Our experiments with rat intestinal loops confirmed the decreased expression of the TJ protein ZO-1 after in vivo stimulation with gliadin, IFN-γ, and/or enterobacteria from CD patients by immunofluorescence and western blot. The second protein band reacting with anti ZO-1 antibodies in some samples, also shown by others [48]–[50], could be a consequence of partial aggregation, complex formation, or external stimuli. In addition, our results demonstrate that these adverse effects are partially restored by B. bifidum IATA-ES2.…”

Section: Discussionmentioning

confidence: 52%

Role of Intestinal Bacteria in Gliadin-Induced Changes in Intestinal Mucosa: Study in Germ-Free Rats

et al. 2011

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Background and AimsCeliac disease (CD) is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins) in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production.Methodology/Principal FindingsChanges in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively) and CD-triggering agents (gliadin and IFN-γ) by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro.Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN)-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection.ConclusionsOur results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa and, consequently, could be involved in the early stages of CD pathogenesis.

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Section: Discussionmentioning

confidence: 52%

Role of Intestinal Bacteria in Gliadin-Induced Changes in Intestinal Mucosa: Study in Germ-Free Rats

et al. 2011

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“…Degradation of occludin by MMP-2/9 is also a feature of blood-brain and blood-retinal barrier disruption in various rat models of type II diabetes and diabetic retinopathy (44,50,62). In other studies, elevated levels of MMP-9 observed in the medial thalamus and brain microvascular endothelium of thiamine-deficient mouse brain (an established model of Wernicke's encephalopathy, which is characterized by petechial hemorrhagic lesions and BBB compromise) have been shown to correlate with reductions of occludin (and ZO-1/2) protein levels and membrane immunolocalization pattern (14). Degradation of occludin (and claudin 5) arising from elevated MMP-9 levels in mouse brain endothelium following azoxymethane-induced acute liver failure (ALF) has also been reported, further corroborating the role of MMP-9 in the vasogenic mechanism of brain edema associated with this disease (19).…”

Section: Proteolytic Degradation (I) Mmp-dependent Proteolysismentioning

confidence: 88%

Occludin: One Protein, Many Forms

Cummins

2012

Molecular and Cellular Biology

343

260

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Intercellular tight junctions (TJs) exhibit a complex molecular architecture involving the regulated cointeraction of cytoplasmic adaptor proteins (e.g., zonula occludens) and integral membrane linker proteins (e.g., occludin and claudins). They provide structural integrity to epithelial and endothelial tissues and create highly polarized barriers essential to homeostatic maintenance within vertebrate physiological systems, while their dysregulation is an established pathophysiological hallmark of many diseases (e.g., cancer, stroke, and inflammatory lung disease). The junctional complex itself is a highly dynamic signaling entity wherein participant proteins constantly undergo a blend of regulatory modifications in response to diverse physiological and pathological cues, ultimately diversifying the overall adhesive properties of the TJ. Occludin, a 65-kDa tetraspan integral membrane protein, contributes to TJ stabilization and optimal barrier function. This paper reviews our current knowledge of how tissue occludin is specifically modified at the posttranscriptional and posttranslational levels in diverse circumstances, with associated consequences for TJ dynamics and epithelial/endothelial homeostasis. Mechanistic concepts such as splice variance and alternate promoter usage, proteolysis, phosphorylation, dimerization, and ubiquitination are comprehensively examined, and possible avenues for future investigation highlighted. (34), is an intramembrane multiprotein complex that provides apical intercelluar connections between adjacent cells in both epithelial and endothelial monolayers. Working in concert with other structurally distinct intercellular junctions (adherens junctions, gap junctions, and desmosomes), TJs provide structural integrity to tissues and create highly polarized barriers with selective paracellular permeability to water, solutes, larger molecules, and other cells, an essential feature of homeostatic maintenance within vertebrate physiological systems. Over the years, additional roles for TJs in cellular differentiation, proliferation, migration, signal transduction, and gene expression have also emerged, highlighting their functional diversity (for reviews, see references 10, 73, and 106), while TJ dysregulation has been associated with the pathogenesis of various diseases, including cancers, stroke, diabetic retinopathy, pulmonary disorders, and inflammatory bowel disease (38). TIGHT JUNCTIONS AND OCCLUDIN T ight junctions. The tight junction (TJ), originally identified in the early 1960s by Farquhar and PaladeThe molecular architecture of the TJ exhibits a complex arrangement of cointeracting cytoplasmic adaptor proteins (e.g., zonula occludens [ZO-1, ZO-2, and ZO-3], as well as 7H6, AF6, vinculin, and cingulin), which mediate the cytoskeletal tethering and cell-cell partnering of transmembrane linker proteins (e.g., occludin, claudins, and junctional adhesion molecules 1, 2, and 3) (1). The overall junctional complex is therefore a highly dynamic signaling entity in which the individual ...

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“…12 Substantial in vivo evidence supports a role for MMP-mediated occludin proteolysis and membrane cleavage. 42,43 This is of particular importance as MMPs have recently been identified as key mediators of intestinal toxicity induced by irinotecan. 9 Al-Dasooqi and colleagues (2010) reported significantly increased small intestinal and serum levels of MMP-9 and MMP-12 following irinotecan.…”

Section: Discussionmentioning

confidence: 99%

“…This correlation has previously been shown in the central nervous system, with MMP-9 levels in brain tissue correlating with reductions in occludin and ZO-1 protein levels. 43,44 Further, MMP inhibition has been shown to ameliorate hypoxicinduced occludin proteolysis. 45 Further studies are now warranted in order to establish the molecular mechanisms of these posttranslational regulations.…”

Section: Discussionmentioning

confidence: 99%