title: Mechanisms of epithelial cell shedding in the Mammalian intestine and maintenance of barrier function.
abstract: The intestinal epithelium forms a barrier between the gut lumen and the body. The barrier is potentially challenged by the high turnover of epithelial cells being shed. Our laboratories have shown that the epithelium is punctuated by discontinuities called "gaps" that have the diameter of an epithelial cell and are devoid of cellular contents. At least a proportion of gaps are formed by the shedding of epithelial cells. These gaps are filled with an unknown substance that maintains local barrier function. Gaps have been identified in the mouse by in vivo confocal microscopy and in humans by confocal endomicroscopy. They can be distinguished from goblet cells by the absence of a nucleus and are found in Math1-/- mice where goblet cells are absent. Cell shedding and gap formation is increased by TNF-alpha. Barrier function is lost after TNF-alpha in approximately 20% of shedding events. These observations suggest that loss of barrier function at sites of cell shedding may be important in intestinal diseases where an increase in epithelial permeability plays a role in pathogenesis.
authors.affiliation: School of Clinical Sciences, University of Liverpool, Liverpool, England. Alastair.watson@liv.ac.uk
authors.forename: Alastair J M
authors.initials: AJ
authors.lastname: Watson
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Duckworth
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Guan
authors.forename: Marshall H
authors.initials: MH
authors.lastname: Montrose
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D014409:Tumor Necrosis Factor-alpha; C500943:Atoh1 protein, mouse