Epithelial Barriers in Homeostasis and Disease

Abstract

Epithelia form barriers that are essential to life. This is particularly true in the intestine, where the epithelial barrier supports nutrient and water transport while preventing microbial contamination of the interstitial tissues. Along with plasma membranes, the intercellular tight junction is the primary cellular determinant of epithelial barrier function. Disruption of tight junction structure, as a result of specific protein mutations or aberrant regulatory signals, can be both a cause and an effect of disease. Recent advances have provided new insights into the extracellular signals and intracellular mediators of tight junction regulation in disease states as well as into the interactions of intestinal barrier function with mucosal immune cells and luminal microbiota. In this review, we discuss the critical roles of the tight junction in health and explore the contributions of barrier dysfunction to disease pathogenesis.

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

“…The epithelial barrier, however, is particularly resilient and is maintained even when excessive epithelial loss occurs [25]. Paracellular permeability is mainly a function of TJ proteins [5,6].…”

“…Content contained in the manuscript has in part been presented at the American Association for the Study of Liver Diseases (AASLD) meeting, Boston, 2010 and as an oral presentation at the European Association for the Study of the Liver (EASL), Barcelona, 2012. composed of various proteins, are essential elements maintaining structural integrity and regulating permeability [5]. The expression and turnover of TJ proteins are influenced by inflammation and oxidative stress [6,7].…”

Rho GTPases in embryonic development

“…This layer of polarized cells that makes up the epithelium serves as both a physical and chemical barrier. 24 An epithelium is typically exposed to 3 different environments: (1) a lumen on its apical side, (2) neighboring cells on its lateral sides, and (3) a basement membrane on its basal side. At the molecular level, these differences in membrane composition begin with the asymmetrical distribution of polarity complexes.…”

“…Many organs consist of tubules transporting vital fluids, serving as both transport and diffusion barriers to selectively enable the absorption of nutrients. 24 Thus, understanding the genesis of these tubules is essential in developmental biology. Many organs develop from simple tubules that branch and ramify into complex treelike structures, 33,34 favoring an increase in the surface area and exchange of nutrients.…”

Editorial - Augmenting Epithelial Barrier Function

“…In fact, our luminal compartments are typically replete with a "rogues' gallery" of microorganisms and antigens, in contrast with the relatively pristine, microorganism-free abluminal compartment -the interstitium and bloodstream. The rogues-gallery of pathogens sitting in our luminal compartments has moreover through the millennia become audaciously adept at getting across our mucosal linings [7]. From their point of view, they have a dodgy existence in a mercurial luminal environment compared to what they may perceive as the climate-controlled, nutritional "Promised Land" on the other side of the mucosa.…”