ArticleDigestive diseases and sciences2012
Intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α.
Article in Digestive diseases and sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Effects of Herb-Partitioned Moxibustion on Autophagy and Immune Activity in the Colon Tissue of Rats with Crohn's Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy.World journal of gastroenterology · 2020Article
- The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders.Frontiers in cell and developmental biology · 2020Review
- Crohn's Disease: Potential Drugs for Modulation of Autophagy.Medicina (Kaunas, Lithuania) · 2019Review
- Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers.International journal of molecular sciences · 2017Article
- Article
- Biological pathways involved in the development of inflammatory bowel disease.Wiener klinische Wochenschrift · 2014Review
- Intestinal epithelium and autophagy: partners in gut homeostasis.Frontiers in immunology · 2013Review
- Autophagy: a new target or an old strategy for the treatment of Crohn's disease?Nature reviews. Gastroenterology & hepatology · 2013Review
- Three isoforms of the Atg16L1 protein contribute different autophagic properties.Molecular and cellular biochemistry · 2013Article
- The role of autophagy in colitis-associated colorectal cancer.Signal transduction and targeted therapyReview
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesGenome-wide association studies have revealed a link between autophagy-related (ATG) genes and susceptibility to Crohn's disease. This suggests underlying involvement of autophagy impairment in the pathogenesis of Crohn's disease. This study was performed to investigate the pathophysiological importance of autophagy impairment in intestinal epithelial cells exposed to TNF-α.
methodsHuman colonic epithelial cells (HT-29) and rat small intestinal epithelial cells (IEC-18) were used. Formation of phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3 (LC3-II) was monitored as a marker of autophagy. Autophagy was inhibited using 3-methyladenine or short interfering RNA targeting ATG5 and ATG16L1.
resultsTNF-α treatment elicited a significant dose-dependent increase in LC3-II protein levels, thus autophagy is induced in the presence of TNF-α. Combined autophagy inhibition and TNF-α treatment induced a marked increase in the number of detached cells and a decrease in activated integrin β1 protein levels. Trypan blue staining indicated 70-80 % of the detached cells were alive, suggesting that these cells became detached not because they were killed but because of dysfunction of cellular adhesion.
conclusionsThis is the first study indicating that intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α. These observations indicate that impairment of autophagy leads to disruption of the intestinal epithelial cell layers in TNF-α-rich environments.
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