Epithelial Cell Shedding and Barrier Function

Williams, Jonathan; Duckworth, Carrie A.; Burkitt, Michael D.; Watson, Alastair; Campbell, Barry J.; Pritchard, D. Mark

doi:10.1177/0300985814559404

Cited by 270 publications

(144 citation statements)

References 84 publications

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“…As noted recently (Williams et al, 2015), remarkably little has been uncovered about homeo-static intestinal extrusion, including whether apoptosis precedes or follows extrusion. Nonetheless, most extruding human small intestine cells are caspase positive, and neighboring cells upregulate phosphorylated myosin light chain (Bullen et al, 2006), reminiscent of the multicellular actomyosin ring that accumulates around extruding apoptotic cells (Rosenblatt et al, 2001).…”

Section: A Force For Evil: Cell Extrusion In Diseasementioning

confidence: 99%

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

2018

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Epithelial tissues robustly respond to internal and external stressors via dynamic cellular rearrangements. Cell extrusion acts as a key regulator of epithelial homeostasis by removing apoptotic cells, orchestrating morphogenesis, and mediating competitive cellular battles during tumorigenesis. Here, we delineate the diverse functions of cell extrusion during development and disease. We emphasize the expanding role for apoptotic cell extrusion in exerting morphogenetic forces, as well as the strong intersection of cell extrusion with cell competition, a homeostatic mechanism that eliminates aberrant or unfit cells. While cell competition and extrusion can exert potent, tumor-suppressive effects, dysregulation of either critical homeostatic program can fuel cancer progression.

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Section: A Force For Evil: Cell Extrusion In Diseasementioning

confidence: 99%

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

2018

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“…Since the chloroform-methanol extracts that inhibited LPS activation of TLR4 demonstrated similar levels of competitive inhibition of LBP and CD14 binding and CL was a major component in those extracts, it was concluded that CL and perhaps other phospholipids were responsible for TLR4 inhibition. Studies in germfree mice revealed that the source of the CL was the host and most likely arose in the intestinal lumen by the turnover of intestinal epithelial cells (39,46). Indeed, studies have shown that intestinal commensal bacteria (19,39,46) and, specifically, LPS can regulate epithelial cell proliferation in a TLR4-dependent fashion in both health and disease (47,48).…”

Section: Discussionmentioning

confidence: 99%

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Coats

Hashim

Paramonov

et al. 2016

Appl Environ Microbiol

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Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCEThe guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders.T he intestinal tract is constantly exposed to the potentially harmful effects of lipopolysaccharide (LPS), commonly referred to as endotoxin. Both internal sources, such as the intestinal microbiome, and external sources, such as food, provide a constant potential for endotoxin-mediated local or systemic injury. Several different innate and adaptive protective mechanisms present in the intestine facilitate a homeostatic relationship with the resident commensal microbiota and buffer food intake such that LPS does not impair normal intestinal tissue functions (1-5).Studies have shown that a major mechanism by which the intestine limits exposure to the potentially harmful effects of LPS is by preventing intestinal LPS-epithelial cell interactions through a physiochemical barrier consisting of a family of glycoproteins referred to as mucins. Mucins provide an effective barricade restrict...

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“…2C; Hopkins et al 2007; Chen et al 2014). In cells about to be extruded from the tip of the villus, ZO-1 and actin reorganize to form a “zipper” along the lateral membrane of live cells surrounding the apoptotic cell until the latter is completely extruded, and then the neighboring cells re-establish contact to reseal the epithelium (Guan et al 2011; Williams et al 2015; Madara 1990; Bullen et al 2006; Marchiando et al 2011). It is critical to maintain junctional integrity during cell migration and cell extrusion to prevent entry points to opportunistic pathogens that would disrupt homeostasis.…”

Section: Intestinal Epithelia Organization and Regulation Of Homeomentioning

confidence: 99%

Cell–Cell Junctions Organize Structural and Signaling Networks

García

Nelson

Chavez

2017

Cold Spring Harb Perspect Biol

345

253

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Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell proliferation and migration. Defects in cell-cell junctions give rise to a wide range of tissue abnormalities that disrupt homeostasis and are common in genetic abnormalities and cancers. Here, we discuss the organization and function of cell-cell junctions primarily involved in adhesion (Tight Junction, Adherens Junction, and Desmosomes) in two different epithelial tissues: a simple epithelium (intestine) and a stratified epithelium (epidermis). Studies in these tissues reveal similarities and differences in the organization and functions of different cell-cell junctions that meet the requirements for the specialized functions of each tissue. We discuss cell-cell junction responses to genetic and environmental perturbations that provide further insights into their roles in maintaining tissue homeostasis.

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Epithelial Cell Shedding and Barrier Function

Cited by 270 publications

References 84 publications

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Cell–Cell Junctions Organize Structural and Signaling Networks

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