Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease

Abstract

Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium establishes a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing intrusion by luminal materials. Intestinal epithelia therefore play a central role in regulating interactions between the mucosal immune system and luminal contents, which include dietary antigens, a diverse intestinal microbiome, and pathogens. The paracellular space is sealed by the tight junction, which is maintained by a complex network of protein interactions. Tight junction dysfunction has been linked to a variety of local and systemic diseases. Two molecularly and biophysically distinct pathways across the intestinal tight junction are selectively and differentially regulated by inflammatory stimuli. This review discusses the mechanisms underlying these events, their impact on disease, and the potential of using these as paradigms for development of tight junction-targeted therapeutic interventions.

Measurement of novel intestinal secretory and barrier pathways and effects of proteases

“…The apical junctional complex that forms between intestinal cells is comprised of tight junctions (TJ) at the top followed by adherens junctions and desmosomes. Integral membrane proteins (claudins, occludin) and junctional complex proteins (zonula occludens, ZOs) regulate TJs . Disruption of the TJ can increase migration of luminal and microbial contents into the subepithelial space and eventually into portosystemic circulation.…”

MicroRNAs in intestinal barrier function, inflammatory bowel disease and related cancers — their effects and therapeutic potentials

“…IB external, mucosal layer is represented by glycosylated mucins and less abundant proteins secreted by goblet cells. Tight junctions that regulate paracellular transport require the presence of proteins such as Claudins, Occludin, MarvelD2/Tricellulin, MarvelD3, Zona occludens (Z0)-1-3 and the regulator of tight junction permeability myosin light chain kinase (MLCK) [5,35]. Paneth cells have a very active autophagy pathway and secret antibacterial peptides, including Lysozyme, RegIIIA and αDefensins such as HD5 and HD6.…”

Making Connections: Guidance Cues and Receptors at Nonneural Cell–Cell Junctions

“…Plaque components include adaptor proteins such as zonula occludens-1 (ZO-1) (Stevenson et al 1986), as well as many downstream signaling components common to axon guidance receptors such as protein kinases, phosphatases, and GTPases (Guillemot et al 2008). For a detailed review of TJs see Buckley and Turner (2017).…”