Mechanisms of Cell Polarity–Controlled Epithelial Homeostasis and Immunity in the Intestine

Klunder, Leon J.; Faber, Klaas Nico; Dijkstra, Gerard; IJzendoorn, Sven C. D. van

doi:10.1101/cshperspect.a027888

Cited by 34 publications

(25 citation statements)

References 121 publications

(163 reference statements)

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“…Closure of the tight junction after acute intestinal injury is a predominant aspect in restoring barrier function and homeostatic functioning [61]. In particular, down regulation of claudin-1, occludin and ZO-1 contributes to increased intestinal permeability that results in cell polarity loss, [62]. In addition, oxidative-stress-induced intestinal permeability is thought to be mediated through the tyrosine phosphorylation of occludin and the redistribution of occludin, ZO-1 and E-cadherin, that could delocalize/disassemble from the TJs [63].…”

Section: Discussionmentioning

confidence: 99%

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

et al. 2020

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Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients’ quality of life. Different strategies are used to treat gastrointestinal mucositis, including products from natural sources. Our study focused on the effect of pomegranate (Punica granatum L.) juice extract on IEC-6 cells, both during inflammatory conditions and following treatment with 5-fluorouracil (5-FU). The polyphenolic profile of pomegranate juice was characterized in detail by Online Comprehensive two dimensional Liquid Chromatography-Mass Spectrometry. The evaluation of pomegranate juice extract in IEC-6 indicates a significant inhibition in proinflammatory factors, such as cytokines release, cyclooxygenase-2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Pomegranate also inhibited oxidative stress and adhesion protein expression. In 5-FU-treated IEC-6, pomegranate also inhibited both inflammatory and oxidative stress parameters and apoptosis. It promoted wound repair and tight junction expression. These results suggest a potential use of pomegranate as an adjuvant in the treatment of intestinal inflammatory and oxidative stress states, which also occur during chemotherapy-induced mucositis.

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Section: Discussionmentioning

confidence: 99%

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

et al. 2020

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“…When the monolayer of intestinal epithelium is injured, such as that which occurs during ischemia/reperfusion injury or exposure to pathogenic microbes such as rotavirus [45,46], detachment of the epithelium from the basement membrane and separation of adjacent epithelial cells from one another due to dysregulation and loss of tight junctional proteins occurs. Furthermore, the loss of polarity-establishing tight junctional proteins results in the loss of cell polarity, which abolishes apical and basolateral positioning of localized molecules such as ion channels/transporters, resulting in their mislocalization [47]. When homeostatic positioning of ion channels and transporters is lost, this can subsequently lead to the dysregulation of a multitude of cellular functions including water absorption/secretion, intracellular and organelle pH, and nutrient absorption.…”

Section: Acute Mechanisms Of Repair In Injured Intestinal Epitheliummentioning

confidence: 99%

The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium

Slifer

Blikslager

2020

IJMS

124

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The intestinal epithelial monolayer forms a transcellular and paracellular barrier that separates luminal contents from the interstitium. The paracellular barrier consists of a highly organized complex of intercellular junctions that is primarily regulated by apical tight junction proteins and tight junction-associated proteins. This homeostatic barrier can be lost through a multitude of injurious events that cause the disruption of the tight junction complex. Acute repair after injury leading to the reestablishment of the tight junction barrier is crucial for the return of both barrier function as well as other cellular functions, including water regulation and nutrient absorption. This review provides an overview of the tight junction complex components and how they link to other plasmalemmal proteins, such as ion channels and transporters, to induce tight junction closure during repair of acute injury. Understanding the components of interepithelial tight junctions and the mechanisms of tight junction regulation after injury is crucial for developing future therapeutic targets for patients experiencing dysregulated intestinal permeability.

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“…For example, the mislocalization of apical proteins in IECs leads to malnutrition, owing to the failure to properly absorb nutrients across the apical membrane, and to potentially fatal diarrheal disorders ( Overeem et al, 2016 ). By contrast, the mislocalization of basolateral proteins correlates with loss of epithelial architecture, cancer development ( Fatehullah et al, 2013 ), and with inflammatory bowel disease ( Klunder et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Intestinal epithelial cell polarity defects in disease: lessons from microvillus inclusion disease

Schneeberger

Roth

Nieuwenhuis

et al. 2018

Disease Models &Amp; Mechanisms

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The intestinal epithelium is a highly organized tissue. The establishment of epithelial cell polarity, with distinct apical and basolateral plasma membrane domains, is pivotal for both barrier formation and for the uptake and vectorial transport of nutrients. The establishment of cell polarity requires a specialized subcellular machinery to transport and recycle proteins to their appropriate location. In order to understand and treat polarity-associated diseases, it is necessary to understand epithelial cell-specific trafficking mechanisms. In this Review, we focus on cell polarity in the adult mammalian intestine. We discuss how intestinal epithelial polarity is established and maintained, and how disturbances in the trafficking machinery can lead to a polarity-associated disorder, microvillus inclusion disease (MVID). Furthermore, we discuss the recent developments in studying MVID, including the creation of genetically manipulated cell lines, mouse models and intestinal organoids, and their uses in basic and applied research.

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Mechanisms of Cell Polarity–Controlled Epithelial Homeostasis and Immunity in the Intestine

Cited by 34 publications

References 121 publications

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium

Intestinal epithelial cell polarity defects in disease: lessons from microvillus inclusion disease

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