Restoration of Barrier Function in Injured Intestinal Mucosa

Abstract

Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.

Less Invasive Corneal Transepithelial Electrical Resistance Measurement Method

“…[37][38][39] Furthermore, TER is also a useful indicator of corneal toxicity. 15,40,41 In general, TER reflects the barrier function of epithelium, with lower corneal TER values indicative of the penetration of greater amounts of electrical current through the damaged superficial cells and tight junctions existing in the epithelium.…”

A novel in vivo corneal trans-epithelial electrical resistance measurement device

“…Because TER is a sensitive, reliable, and versatile test of barrier function, it is used to study the integrity of tissues and cell sheets such as the intestinal epithelium and Madin-Darby canine kidney cells (Balda et al, 1996: Blikslager et al, 2007: Moyes et al, 2007. Furthermore, TER is also a useful indicator of corneal toxicity (Chetoni et al, 2003.…”

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

“…Under physiological conditions the epithelial monolayer is renewed every 5-7 days (44). This regeneration process begins with the migration of neighboring cells over the injured area, which is known as epithelial restitution (6). Additionally, the barrier depends on the proliferation and differentiation of new cells to compensate the loss of cells within the wounded areas.…”