| Occludin Regulates Macromolecule Flux across the Intestinal Epithelial Tight Junction Barrier. | |
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MedLine Citation:
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PMID: 21415414 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Defective intestinal epithelial tight junction (TJ) barrier has been shown to be an important pathogenic factor contributing to the development of intestinal inflammation. The expression of occludin is markedly decreased in intestinal permeability disorders, including in Crohn's disease, ulcerative colitis, and celiac disease, suggesting that the decrease in occludin expression may play a role in the increase in intestinal permeability. The purpose of this study was to delineate the involvement of occludin in intestinal epithelial TJ barrier by selective knock-down of occludin in an in-vitro (filter-grown Caco-2 monolayers) and in-vivo (recycling perfusion of mouse intestine) intestinal epithelial models. Our results indicated that occludin siRNA transfection causes an increase in trans-epithelial flux of various-sized probes including urea, mannitol, inulin and dextran across the Caco-2 monolayers, without affecting the trans-epithelial resistance. The increase in relative flux rate was progressively greater for larger sized probes, indicating that occludin depletion has greatest effect on the flux of large macromolecules. SiRNA induced knock-down of occludin in mouse intestine in-vivo also caused an increase in intestinal permeability to dextran but did not affect intestinal tissue trans-epithelial resistance. In conclusion, these results show for the first time that occludin depletion in intestinal epithelial cells in-vitro and in-vivo leads to a selective or preferential increase in macromolecule flux; suggesting that occludin plays a crucial role in the maintenance of TJ barrier through the large channel TJ pathway, the pathway responsible for the macromolecule flux. |
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Authors:
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Rana Al-Sadi; Khaldun Khatib; Shuhong Guo; Dongmei Ye; Moustafa Youssef; Thomas Y Ma |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-17 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: - ISSN: 1522-1547 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of New Mexico. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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