期刊
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
卷 3, 期 2, 页码 150-162出版社
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2016.12.006
关键词
Celiac Sprue; Gluten-Sensitive Enteropathy; Tight Junction; Epithelial Polarity; Partitioning-Defective Proteins; alpha-Gliadin 33mer
资金
- Deutsche Forschungsgemeinschaft [SPP 1656, SCHU 559/11-2, FR 652/12-1]
- Charite-Universitatsmedizin Berlin
- Berlin Institute of Health
Recent findings have suggested that the mucosal barrier is a primary focus of disease activity in celiac disease. Alongside the well-established remodeling of the small intestinal architecture, focal epithelial barrier defects occur with increased apoptosis and an altered tight junction-mediated permeability. Barrier-forming claudins are down-regulated while the channel-forming claudins are up-regulated, both causing a loss of ions and water to the gut lumen. An intimately regulated transcellular passage of gliadin peptides is needed for celiac disease development. As a central organizer of proteins related to barrier function, the role of epithelial polarity regulators is discussed. In celiac disease (CD) a T-cell-mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an underrated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed.
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