Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application.
The intestinal epithelium is faced with the complex task of providing a barrier while also allowing nutrient and water absorption. The frequency with which these processes are disrupted in disease can be taken as evidence of their importance. It is therefore of interest to define the mechanisms of altered intestinal barrier and transport function and develop means to correct disease-associated defects. Over the past 10 years, some of the molecular events underlying physiological epithelial barrier regulation have been described. Remarkably, recent advances have shown that activation of the same mechanisms is central to barrier dysfunction in both in vitro and in vivo models of disease. Although the contribution of barrier dysfunction to pathogenesis of chronic disease remains incompletely understood, it is now clear that cytoskeletal regulation of barrier function is both an important pathogenic process and that targeted inhibition of myosin light chain kinase, which affects this cytoskeleton-dependent tight junction dysfunction, is an attractive candidate for therapeutic intervention.
Turner
Jerrold R
JR
Department of Pathology, The University of Chicago, 5841 South Maryland Ave., MC 1089, Chicago, IL 60637, USA. jturner@bsd.uchicago.edu
D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D003599:Cytoskeleton / Q000502:physiology; D003967:Diarrhea / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000502:physiology* / Q000503:physiopathology; D008954:Models, Biological; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000199:Actins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D009219:Myosin-Light-Chain Kinase