| Intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α. | |
| | |
MedLine Citation:
|
PMID: 22466076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND AND OBJECTIVES: Genome-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. METHODS: Human 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. RESULTS: TNF-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. CONCLUSIONS: This 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. |
| | |
Authors:
|
Masaya Saito; Tatsuro Katsuno; Tomoo Nakagawa; Toru Sato; Yoshiko Noguchi; Sayuri Sazuka; Keiko Saito; Makoto Arai; Koutaro Yokote; Osamu Yokosuka |
Related Documents
:
|
9689056 - Unusual proliferation arrest and transcriptional control properties of a newly discover... 10413586 - The hmg protein t160 colocalizes with dna replication foci and is down-regulated during... 2420376 - Immunocytochemical localization of relaxin in corpora lutea of sows throughout the estr... 9755166 - An essential protease involved in bacterial cell-cycle control. 9873956 - The effect of intermittent injections of cck-8s and the cck-a receptor antagonist devaz... 8164056 - Gfap expression in the subcutaneous tumors of immature glial cell line (hits glioma) de... |
Publication Detail:
|
Type: Journal Article Date: 2012-03-31 |
Journal Detail:
|
Title: Digestive diseases and sciences Volume: 57 ISSN: 1573-2568 ISO Abbreviation: Dig. Dis. Sci. Publication Date: 2012 Aug |
Date Detail:
|
Created Date: 2012-07-26 Completed Date: 2012-10-16 Revised Date: 2013-01-30 |
Medline Journal Info:
|
Nlm Unique ID: 7902782 Medline TA: Dig Dis Sci Country: United States |
Other Details:
|
Languages: eng Pagination: 2022-30 Citation Subset: AIM; IM |
Affiliation:
|
Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antigens, CD29 / metabolism Autophagy* Cell Adhesion Crohn Disease / etiology Epithelial Cells / cytology GTP-Binding Proteins / metabolism HT29 Cells Humans Intestinal Mucosa / cytology, physiology* Rats Tumor Necrosis Factor-alpha / physiology* |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD29; 0/Tumor Necrosis Factor-alpha; EC 3.6.1.-/Atg16L1 protein, rat; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reverse transmission along the ossicular chain in gerbil.
Next Document: Undertreatment of Asian Chronic Hepatitis B Patients on the Basis of Standard Guidelines: A Communit...