Role of autophagy in the regulation of epithelial cell junctions

Nighot, Prashant K.; Ma, Thomas

doi:10.1080/21688370.2016.1171284

Cited by 33 publications

(30 citation statements)

References 107 publications

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“…In this study, we show that antibiotics activate autophagy, as evidenced by decreased P62 expression and increased LC3-II/LC3-I ratio and Atg5 expression. Although autophagy activation has been reported to be closely associated with intestinal barrier dysfunction [16,51,52], the precise role of autophagy activation in regulating barrier function is still controversial. Some studies have demonstrated that autophagy maintained intestinal or endothelial barrier [53,54].…”

Section: Discussionmentioning

confidence: 99%

Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

et al. 2019

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Tight junction barrier is critical to intestinal homeostasis. Applying antibiotics to treat infections is common in clinical practice, which may affect intestinal microbiota. Intestinal microbiota dysbiosis is involved in the occurrence of some gastrointestinal diseases. Therefore, this study was aimed to investigate the influence of antibiotics on intestinal tight junction barrier and the possible underlying mechanisms. Healthy adult female C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail for 14 days. 16S rDNA Illumina sequencing and headspace gas chromatography-mass spectrometry (HS-GC/MS) were respectively used to analyze microbial community and to detect short-chain fatty acids (SCFAs) contents. In vivo intestinal paracellular permeability to fluorescein isothiocyanate-dextran (FITC-dextran) was measured. Protein expression was determined by immunoblotting. Immunofluoresence was applied to observe the distributions of ZO-1, LC3B and ASC. Antibiotics remarkably altered intestinal microbiota composition in healthy mice, accompanying reduced SCFAs’ concentrations. In addition, the intestinal tight junction barrier was disrupted by antibiotic treatment, as evidenced by increased intestinal paracellular permeability to FITC-dextran, decreased tight junction protein expressions, and disrupted ZO-1 morphology. Furthermore, NLRP3 inflammasome and autophagy were activated by antibiotic treatment. In conclusion, intestinal epithelial tight junction barrier dysfunction induced by antibiotics is associated with intestinal microbiota dysbiosis, activated NLRP3 inflammasome and autophagy in mice.

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Section: Discussionmentioning

confidence: 99%

Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

et al. 2019

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“…CDH1 forms also hetero-oligomers with CDH2/ N-cadherin, which interact stronger, mediating contacts of different cell types. Autophagy ensures optimal cell growth via regulating the abundance of CDH1, a protein involved in CTNNB1 (catenin beta 1)-WNT signaling[52][53][54] (Figure 2). SNXs (sorting nexins), a class of peripheral membrane proteins important for endosomal sorting, can oligomerize via their Bin/Amphiphysin/Rvs (BAR) domains to perform vesicle to tubular membrane remodeling.…”

mentioning

confidence: 99%

Protein complexes and neighborhoods driving autophagy

Sankar

Dengjel

2020

Autophagy

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Autophagy summarizes evolutionarily conserved, intracellular degradation processes targeting cytoplasmic material for lysosomal degradation. These encompass constitutive processes as well as stress responses, which are often found dysregulated in diseases. Autophagy pathways help in the clearance of damaged organelles, protein aggregates and macromolecules, mediating their recycling and maintaining cellular homeostasis. Protein-protein interaction networks contribute to autophagosome biogenesis, substrate loading, vesicular trafficking and fusion, protein translocations across membranes and degradation in lysosomes. Hypothesis-free proteomic approaches tremendously helped in the functional characterization of protein-protein interactions to uncover molecular mechanisms regulating autophagy. In this review, we elaborate on the importance of understanding protein-protein-interactions of varying affinities and on the strengths of mass spectrometry-based proteomic approaches to study these, generating new mechanistic insights into autophagy regulation. We discuss in detail affinity purification approaches and recent developments in proximity labeling coupled to mass spectrometry, which uncovered molecular principles of autophagy mechanisms. Abbreviations : AMPK: AMP-activated protein kinase; AP-MS: affinity purification-mass spectrometry; APEX2: ascorbate peroxidase-2; ATG: autophagy related; BioID: proximity-dependent biotin identification; ER: endoplasmic reticulum; GFP: green fluorescent protein; iTRAQ: isobaric tag for relative and absolute quantification; MS: mass spectrometry; PCA: protein-fragment complementation assay; PL-MS: proximity labeling-mass spectrometry; PtdIns3P: phosphatidylinositol-3-phosphate; PTM: posttranslational modification; PUP-IT: pupylation-based interaction tagging; RFP: red fluorescent protein; SILAC: stable isotope labeling by amino acids in cell culture; TAP: tandem affinity purification; TMT: tandem mass tag.

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“…Epithelial cells are connected through tight junctions, adherens junctions and gap junctions, and continuous endocytosis and recycling of junctional proteins occur over the cell membrane. During inflammation, connexin degradation can cause nutrient starvation [65]. Epithelial cells in different organs express Cx43 and have gap junction communication [66], and similar properties have been demonstrated between tenocytes in Achilles tendons [67] (Fig.…”

Section: Gap Junction-coupled Cellsmentioning

confidence: 78%

Low-grade inflammation causes gap junction-coupled cell dysfunction throughout the body, which can lead to the spread of systemic inflammation

Hanssoń

Skiöldebrand

2019

Scandinavian Journal of Pain

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Background and aims Gap junction-coupled cells form networks in different organs in the body. These networks can be affected by inflammatory stimuli and become dysregulated. Cell signaling is also changed through connexin-linked gap junctions. This alteration affects the surrounding cells and extracellular matrix in organs. These changes can cause the spread of inflammatory substances, thus affecting other network-linked cells in other organs in the body, which can give rise to systemic inflammation, which in turn can lead to pain that can turn into chronic. Methods This is a review based on literature search and our own research data of inflammatory stimuli that can affect different organs and particularly gap-junction-coupled cells throughout the body. Conclusions A remaining question is which cell type or tissue is first affected by inflammatory stimuli. Can endotoxin exposure through the air, water and body start the process and are mast cells the first target cells that have the capacity to alter the physiological status of gap junction-coupled cells, thereby causing breakdown of different barrier systems? Implications Is it possible to address the right cellular and biochemical parameters and restore inflammatory systems to a normal physiological level by therapeutic strategies?

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Role of autophagy in the regulation of epithelial cell junctions

Cited by 33 publications

References 107 publications

Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

Protein complexes and neighborhoods driving autophagy

Low-grade inflammation causes gap junction-coupled cell dysfunction throughout the body, which can lead to the spread of systemic inflammation

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