Cleavage of transmembrane junction proteins and their role in regulating epithelial homeostasis

Nava, Porfirio; Kamekura, Ryuta; Nusrat, Asma

doi:10.4161/tisb.24783

Cited by 36 publications

(31 citation statements)

References 145 publications

(219 reference statements)

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“…In the inflamed gut, this is likely to be accelerated by the protease-mediated cleavage of adhesive AJ and DM proteins. 160 For example, IL1B and TNF promote the cleavage of the extracellular domains of intestinal epithelial desmoglein 2, desmocollin 2, and E-cadherin in a disintegrin and metalloproteinase domain containing protein 10 and matrix metalloproteinase 9–dependent manner. 120 Such cadherin-cleaved ectodomains have signaling properties that influence epithelial homeostasis.…”

Section: Effects Of Inflammationmentioning

confidence: 99%

Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

2016

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The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation.

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Section: Effects Of Inflammationmentioning

confidence: 99%

Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

2016

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“…One reported mechanism involves proteolytic degradation of E-cadherin. E-cadherin degradation was observed during colonization of intestinal epithelium by enteric pathogens such as Bacteroides fragilis and Campylobacter jejuni [62, 63], or following neutrophil infiltration in the inflamed mucosa [64-66]. Invading bacteria and activated immune cells release different proteases that cause shedding of the E-cadherin ectodomain, thereby decreasing the concentration of adhesion competent protein at the plasma membrane.…”

Section: Regulation Of Aj and Tj Protein Expression In Inflamed Inmentioning

confidence: 99%

Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms

Lechuga

Ivanov

2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

202

164

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The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders.

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“…125 Increased MMP activity influences epithelial adhesion and is also associated with degradation of growth factors and other peptides involved in the repair process, 126 and ultimately results in immune-mediated tissue injury such as seen in inflammatory bowel disease. 127–129 Furthermore, inflammatory mediators have been reported to influence migration of fibroblasts and epithelial cells and therefore impact the rate of wound closure in chronic intestinal inflammation. 130,131 Altogether these events lead to instability of the extracellular matrix and prevent interactions between cells and matrix proteins that are essential for cell migration and wound resealing.…”

Section: Chronic Inflammation and Delayed Wound Healingmentioning

confidence: 99%

Wound repair: role of immune–epithelial interactions

Leoni¹,

Neumann²,

et al. 2015

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The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair.

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Cleavage of transmembrane junction proteins and their role in regulating epithelial homeostasis

Cited by 36 publications

References 145 publications

Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms

Wound repair: role of immune–epithelial interactions

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