Molecular basis of epithelial barrier regulation - From basic mechanisms to clinical application

被引:449
作者
Turner, Jerrold R. [1 ]
机构
[1] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
关键词
D O I
10.2353/ajpath.2006.060681
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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 die mechanisms of altered intestinal barrier and transport function and develop means to correct disease-associated defects. over the past 10 years, some of die 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.
引用
收藏
页码:1901 / 1909
页数:9
相关论文
共 75 条
[71]   CD45RO EXPRESSION ON CIRCULATING CD19(+) B-CELLS IN CROHNS-DISEASE CORRELATES WITH INTESTINAL PERMEABILITY [J].
YACYSHYN, BR ;
MEDDINGS, JB .
GASTROENTEROLOGY, 1995, 108 (01) :132-137
[72]   Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells [J].
Yu, ASL ;
McCarthy, KM ;
Francis, SA ;
McCormack, JM ;
Lai, J ;
Rogers, RA ;
Lynch, RD ;
Schneeberger, EE .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2005, 288 (06) :C1231-C1241
[73]   Enteropathogenic Escherichia coli-induced myosin light chain phosphorylation alters intestinal epithelial permeability [J].
Yuhan, R ;
Koutsouris, A ;
Savkovic, SD ;
Hecht, G .
GASTROENTEROLOGY, 1997, 113 (06) :1873-1882
[74]   Ezrin regulates NHE3 translocation and activation after Na+-glucose cotransport [J].
Zhao, HR ;
Shiue, H ;
Palkon, S ;
Wang, YM ;
Cullinan, P ;
Burkhardt, JK ;
Musch, MW ;
Chang, EB ;
Turner, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (25) :9485-9490
[75]   A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease [J].
Zolotarevsky, Y ;
Hecht, G ;
Koutsouris, A ;
Gonzalez, DE ;
Quan, C ;
Tom, J ;
Mrsny, RJ ;
Turner, JR .
GASTROENTEROLOGY, 2002, 123 (01) :163-172