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World J Gastrointest Pathophysiol. Nov 15, 2013; 4(4): 94-99
Published online Nov 15, 2013. doi: 10.4291/wjgp.v4.i4.94
Intestinal barrier: Molecular pathways and modifiers
Min Kyung Jeon, Christina Klaus, Elke Kaemmerer, Nikolaus Gassler
Min Kyung Jeon, Christina Klaus, Elke Kaemmerer, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
Author contributions: Jeon MK and Gassler N designed and wrote the article; Klaus C and Kaemmerer E critical reviewed the literature and made technical notes.
Correspondence to: Nikolaus Gassler, MA, Professor, Institute of Pathology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.
Telephone: +49-241-8088897 Fax: +49-241-8082439
Received: June 24, 2013
Revised: August 28, 2013
Accepted: September 3, 2013
Published online: November 15, 2013

The gastrointestinal tract is frequently challenged by pathogens/antigens contained in food and water and the intestinal epithelium must be capable of rapid regeneration in the event of tissue damage. Disruption of the intestinal barrier leads to a number of immune-mediated diseases, including inflammatory bowel disease, food allergy, and celiac disease. The intestinal mucosa is composed of different types of epithelial cells in specific barrier functions. Epithelial cells control surface-associated bacterial populations without disrupting the intestinal microflora that is crucial for host health. They are also capable of modulating mucosal immune system, and are thus essential in maintaining homeostasis in the gut. Thus, the regulation of intestinal epithelial homeostasis is crucial for the maintenance of the structure of the mucosa and the defensive barrier functions. Recent studies have demonstrated that multiple molecular pathways are involved in the regulation of intestinal epithelial cell polarity. These include the Wnt, Notch, Hippo, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog pathways, most of which were identified in lower organisms where they play important roles during embryogenesis. These pathways are also used in adult organisms to regulate multiple self-renewing organs. Understanding the interactions between these molecular mechanisms and intestinal barrier function will therefore provide important insight into the pathogenesis of intestinal-based immune-mediated diseases.

Keywords: Intestinal epithelium, Mucosal barrier, Homeostasis, Molecular pathways, Immune-mediated disease

Core tip: The pathogenesis of gastrointestinal diseases is associated with important molecular pathways such as Wnt, Notch, Hippo, transforming growth factor-β/bone morphogenetic protein or Hedgehog in controlling cell-fate determination. Here, we discuss how they contribute to homeostasis of intestinal epithelium.