Claudins in Intestinal Function and Disease

摘要

Epithelial tight junction (TJ) strands consist of TJ proteins including occludin, JAM, claudins, and tricellulin. Especially the members of the claudin family are key determinants in the regulation of epithelial barrier function in the intestine. Multiple differences in claudin expression along the gastrointestinal (GI) tract define the epithelial barrier properties in each particular intestinal segment and can—when changed contribute to the pathophysiology of different diseases. Such changes in TJ protein composition can be due to expression regulation from the gene, modified TJ protein degradation, regulation of TJ assembly/disassembly via the cytoskeleton or by effects on TJ protein endocytosis. Various regulatory mechanisms are responsible for alterations in claudin expression reported here in detail for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), for celiac disease as well as for intestinal infections like norovirus, enteropathogenic Escherichia col, Campylobacter, or Giardia lamblia. These analyses revealed that specific modifications in claudin expression and distribution are found in diseases in combination with their distinct inflammatory appearance, as a result of which leak-flux diarrhea can be induced or the entry of luminal antigens into the mucosa is facilitated, which perpetuates or can even initiate inflammatory processes.