Cell death in the colonic epithelium during inflammatory bowel diseases

Chen, Lina; Park, Sun Mi; Turner, Jerrold R.; Marynen, Peter

doi:10.1002/ibd.21191

Cited by 31 publications

(26 citation statements)

References 73 publications

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“…Results in Figs. 4 and 5 suggest that changes in shape and size of shedding cells are more prominent than any changes in surrounding cells within the epithelial layer. The constancy of the cells neighboring the extruding cell does not support the idea that the neighboring cells produce local force to push the shedding cell out, although this possibility cannot be fully ruled out on the basis of our measurements.…”

Section: Discussionmentioning

confidence: 99%

“…In other studies, experimentally induced epithelial wounds cause F-actin and myosin-II to accumulate at tight junctions and form a "purse-string" that closes the wound to restore epithelial barrier function (2,5). Phosphorylated myosin light chain has been observed at sites of physiological cell shedding (3,33) and in inflammatory bowel disease tissues (4,26), suggesting that tight junction regulation is likely impacted during cell extrusion. Intriguingly, the tight junction scaffold protein, zonula occludens protein-1 (ZO-1), recently shown to render structural firmness and impermeability to the junction, is a link between occludin and the actin cytoskeleton (7,8,24).…”

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confidence: 95%

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Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Guan

Watson

Marchiando

et al. 2011

American Journal of Physiology-Cell Physiology

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We questioned how tight junctions contribute to intestinal barrier function during the cell shedding that is part of physiological cell renewal. Intravital confocal microscopy studied the jejunal villus epithelium of mice expressing a fluorescent zonula occludens 1 (ZO-1) fusion protein. Vital staining also visualized the cell nucleus (Hoechst staining) or local permeability to luminal constituents (Lucifer Yellow; LY). In a cell fated to be shed, ZO-1 redistributes from the tight junction toward the apical and then basolateral cell region. ZO-1 rearrangement occurs 15 Ϯ 6 min (n ϭ 28) before movement of the cell nucleus from the epithelial layer. During cell extrusion, permeation of luminal LY extends along the lateral intercellular spaces of the shedding cell only as far as the location of ZO-1. Within 3 min after detachment from the epithelial layer, nuclear chromatin condenses. After cell loss, a residual patch of ZO-1 remains in the space previously occupied by the departed cell, and the size of the patch shrinks to 14 Ϯ 2% (n ϭ 15) of the original cell space over 20 min. The duration of cell shedding measured by nucleus movement (14 Ϯ 1 min) is much less than the total duration of ZO-1 redistribution at the same sites (45 Ϯ 2 min). In about 15% of cell shedding cases, neighboring epithelial cells also undergo extrusion with a delay of 5-10 min. With the use of normal mice, ZO-1 immunofluorescent staining of fixed tissue confirmed ZO-1 redistribution and the presence of ZO-1 patches beneath shedding cells. Immunostaining also showed that redistribution of ZO-1 occurred without corresponding mixing of apical and basolateral membrane domains as marked by ezrin or Ecadherin. ZO-1 redistribution is the earliest cellular event yet identified as a herald of physiological cell shedding, and redistribution of tight junction function along the lateral plasma membrane sustains epithelial barrier during cell shedding. jejunum; fluorescent protein; intestinal permeability; intravital microscopy; laser scanning confocal microscopy; multiphoton microscopy

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Guan

Watson

Marchiando

et al. 2011

American Journal of Physiology-Cell Physiology

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“…The levels of PPID and ASK1 did not show significant differences between the different stages of the disease and the control patients. Among the studies performed to explain the molecular mechanism responsible for granting lymphocytes apoptosis resistance, we can highlight those studying the apoptotic signaling pathways [18]. FASR belongs to the superfamily of tumor necrosis factor receptors, and its most important signaling function is to participate in the induction of apoptosis by ligand recognition of FASL and assembly of all proteins that form the death-inducing signaling complex: the Fas-associated protein with death domain, the procaspases 8/10, and the c-FLIP [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

et al. 2018

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Background/Aims: Increased oxidative stress and decreased immune cell apoptosis have been reported to be important factors in the pathogenesis of Crohn’s disease (CD). Our aim was to characterize the genetic expression of molecules implicated in the regulation of oxidative stress and apoptosis in peripheral white mononuclear cells of 18 healthy volunteers (controls) and 20 patients at the onset of CD (active CD [aCD]): 10 who achieved remission (inactive CD [iCD]) and 10 who did not present a complete and deep response to treatment (aCD-T). Methods: mRNA expression was measured by the Agena MassARRAY quantitative gene expression analysis application. The genes analyzed were Fas-receptor (FASR), Fas-ligand (FASL), signal transducer and activator of transcription 1 (STAT1), nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB1), apoptosis signal-regulating kinase 1 (ASK1), serine/threonine-protein kinase H1 (PSKH1), ATP-binding cassette sub-family B1 (ABCB1) and peptidylprolyl isomerase D (PPID). Results: During a CD flare, we found specific upregulated expression of the genes STAT1 and PSKH1, whereas ABCB1 and FASL were downregulated. In the patients with iCD, FASR and NFKB1 were upregulated. The expression levels of NFKB1, STAT1 and ABCB1 did not show any difference in patients with aCD at the onset of the disease and after treatment (aCD-T). The expression levels of PPID and ASK1 did not show any differences in the patients with aCD, iCD and the controls. We have also reviewed the cellular function and role of these genes in CD. Conclusions: These findings contribute to improving the understanding of the pathogenesis of CD and highlight potential genes involved.

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“…However, accumulating evidences support a significant role for Fas in alternative non-death signaling leading to cell survival, proliferation, epithelial-mesenchymal transition, cancer growth and metastasis in some context. [3][4][5] Such conditional multi-signaling of Fas has been well demonstrated in colon cancer model. 6,7 We demonstrated that Fas and FasL are constitutively modified by S-palmitoylation, a reversible post-translational modification that consists in the addition of a palmitic acid on the cysteine residue through a thiol linkage.…”

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confidence: 92%

Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability

et al. 2014

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The death receptor Fas undergoes a variety of post-translational modifications including S-palmitoylation. This protein acylation has been reported essential for an optimal cell death signaling by allowing both a proper Fas localization in cholesterol and sphingolipid-enriched membrane nanodomains, as well as Fas high-molecular weight complexes. In human, S-palmitoylation is controlled by 23 members of the DHHC family through their palmitoyl acyltransferase activity. In order to better understand the role of this post-translational modification in the regulation of the Fas-mediated apoptosis pathway, we performed a screen that allowed the identification of DHHC7 as a Fas-palmitoylating enzyme. Indeed, modifying DHHC7 expression by specific silencing or overexpression, respectively, reduces or enhances Fas palmitoylation and DHHC7 co-immunoprecipitates with Fas. At a functional level, DHHC7-mediated palmitoylation of Fas allows a proper Fas expression level by preventing its degradation through the lysosomes. Indeed, the decrease of Fas expression obtained upon loss of Fas palmitoylation can be restored by inhibiting the lysosomal degradation pathway. We describe the modification of Fas by palmitoylation as a novel mechanism for the regulation of Fas expression through its ability to circumvent its degradation by lysosomal proteolysis. Cell Death and Differentiation (2015) We demonstrated that Fas and FasL are constitutively modified by S-palmitoylation, a reversible post-translational modification that consists in the addition of a palmitic acid on the cysteine residue through a thiol linkage. [8][9][10] The palmitoylation of a protein can affect its interactions with its surrounding membrane lipids and proteins, therefore impacting certain properties such as association with specific membrane domains, trafficking between cell compartments or stability. [11][12][13] The palmitoylation reaction is catalyzed by the conserved DHHC (aspartate-histidine-histidine-cysteine) family of enzymes, which are characterized by the specific DHHC motif required for the palmitoyl acyltransferase (PAT) activity. 14 In human, the 23 members of the DHHC family described are localized to the distinct intracellular membrane compartments, mainly the Golgi apparatus and the endoplasmic reticulum where palmitoylation likely occurs. 14,15 Since their discovery in 2002, increasing numbers of DHHC-substrate pairs have been identified allowing a deeper comprehension of palmitoylation regulation. 16 Fas palmitoylation occurs on an intracellular cysteine adjacent to the transmembrane domain (cysteine 199 in human) and is critical for its ability to trigger cell death. 8,9 At the molecular level, we and others already reported that the pro-death role of Fas palmitoylation relies on (i) the formation of supramolecular Fas aggregates 9 and (ii) Fas targeting in nanodomains enriched in cholesterol and glycosphingolipids, which is a prerequisite for proper activation of Fas-induced cell death. 8,[17][18][19][20][21] In these domains and upon FasL...

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Cell death in the colonic epithelium during inflammatory bowel diseases

Cited by 31 publications

References 73 publications

Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability

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