2019
DOI: 10.1152/ajpcell.00246.2018
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Intestinal epithelial tight junction barrier regulation by autophagy-related protein ATG6/beclin 1

Abstract: A defective tight junction (TJ) barrier is a key pathogenic factor for inflammatory bowel disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelial TJ barrier function. Autophagy-related protein-6 (ATG6/beclin 1), a key protein in the autophagy pathway, also plays a role in the endocytic pathway. The constitutive role of beclin 1 in the intestinal TJ barrier is not known. In Caco-2 cells, beclin 1 was found to be coimmunoprecipitated with the TJ protein occlud… Show more

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Cited by 47 publications
(32 citation statements)
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“…We also observed a significant increase in the expression of the TJ protein occludin in HT-29/B6-GR/MR cell monolayers after infection with C. concisus. This could be a result of host cell autophagy modulation required for intracellular survival of C. concisus [38,39]. Besides, occludin was demonstrated not to affect the ionic barrier properties of intestinal epithelia in an occludin knockout mouse model, since the transepithelial electrical resistance did not differ between occludin-deficient mice and their wild-type littermates [40,41].…”
Section: Discussionmentioning
confidence: 95%
“…We also observed a significant increase in the expression of the TJ protein occludin in HT-29/B6-GR/MR cell monolayers after infection with C. concisus. This could be a result of host cell autophagy modulation required for intracellular survival of C. concisus [38,39]. Besides, occludin was demonstrated not to affect the ionic barrier properties of intestinal epithelia in an occludin knockout mouse model, since the transepithelial electrical resistance did not differ between occludin-deficient mice and their wild-type littermates [40,41].…”
Section: Discussionmentioning
confidence: 95%
“…One important family of components that comprise the barrier are TJs, which consist of several transmembrane and cytoplasmic proteins, such as claudins, zonula occludens-1 (ZO-1), and junctional adhesion molecule A (JAM-A). TJs stabilize intercellular connections, maintain cell polarity, form specific apical domains and are involved in the regulation of key cellular functions, such as proliferation, differentiation and migration [ 21 , 22 ]. Regarding the levels of the TJs expression in intestinal diseases, the data are conflicting as both, increases and decreases in the expression of various TJs have been reported [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”
Section: Discussionmentioning
confidence: 99%
“…Such opposing findings may be the result of at least two factors. First, alternations in the expression of TJs may be secondary to the underlying intestinal diseases of various origins [ 21 , 22 , 24 ]. Second, some intestinal diseases may result from genetically determined alterations in the expression of TJs [ 28 , 29 , 30 ].…”
Section: Discussionmentioning
confidence: 99%
“…The autophagic process and the genes that regulate autophagy are crucial for intestinal homeostasis. Autophagy is required for the maintenance of tight junction integrity, gutcommensal homeostasis, and control of invasive bacteria at the intestinal epithelium (Bel et al, 2017, Benjamin et al, 2013, Burger et al, 2018, Cadwell et al, 2008, Cadwell et al, 2009, Lee et al, 2016a, Matsuzawa-Ishimoto et al, 2017, Nighot et al, 2015, Patel et al, 2013, Wong et al, 2019, Wu, Wang et al, 2017. Multiple lines of evidence also suggest autophagy regulates inflammatory cytokines (Castillo et al, 2012, Dupont et al, 2011, Lee, Foote et al, 2016b, Merkley, Chock et al, 2018, Saitoh, Fujita et al, 2008.…”
Section: Discussionmentioning
confidence: 99%
“…Autophagy has proven critical for intestinal homeostasis. Defects in the autophagic pathway, specifically in intestinal epithelial cell lineages, results in increased intestinal permeability and Paneth and Goblet cell (GC) dysfunction (Cadwell, Liu et al, 2008, Cadwell, Patel et al, 2009, Matsuzawa-Ishimoto, Shono et al, 2017, Nighot, Hu et al, 2015, Patel, Miyoshi et al, 2013, Wong, Ganapathy et al, 2019.…”
Section: Introductionmentioning
confidence: 99%