Tight junction proteins in gastrointestinal and liver disease

Abstract

Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV—one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

Pharmacological activation of ERβ by arctigenin maintains the integrity of intestinal epithelial barrier in inflammatory bowel diseases

“…Separating epithelial cells are various junctions, including tight junction (TJ), adherence junction, and gap junction . Among which, TJ plays a crucial role in maintaining the intestinal epithelial barrier integrity . The dysfunction of TJ increases the paracellular permeability.…”

“…35 Among which, TJ plays a crucial role in maintaining the intestinal epithelial barrier integrity. 36,37 The dysfunction of TJ increases the paracellular permeability. The entry of luminal pro-inflammatory molecules induces mucosal immune system activation, resulting in sustained inflammation and tissue injury.…”

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

“…The loss of epithelial barrier integrity in EoE is attributed to the downregulation of important structural proteins in the inflamed mucosa including tight junction (TJ) proteins . The tight junction (TJ) complex is a dynamic structure comprised of transmembrane claudins, occludin, and cytosolic proteins (ie, zonula occludens‐1, zonula occludens‐2, and zonula occludens‐3), which connect the TJ to the cytoskeleton . Expression of occludin and claudin‐1 is decreased in biopsy tissue of EoE patients both before and after treatment with swallowed corticosteroid .…”

“…2,5,7 The tight junction (TJ) complex is a dynamic structure comprised of transmembrane claudins, occludin, and cytosolic proteins (ie, zonula occludens-1, zonula occludens-2, and zonula occludens-3), which connect the TJ to the cytoskeleton. [8][9][10] Expression of occludin and claudin-1 is decreased in biopsy tissue of EoE patients both before and after treatment with swallowed corticosteroid. 2 In addition to tight junctions, multiple structural proteins contribute to the integrity and stratification of the esophageal epithelial barrier.…”

β‐Elemene inhibits peritoneal metastasis of gastric cancer cells by modulating FAK/Claudin‐1 signaling

“…Claudin-1 is a critical component of tight junctions and plays a crucial role in regulating proliferation and metastasis (Zeisel, Dhawan, Mingming Deng and Ye Zhang contributed equally to this work. & Baumert, 2018). Several studies have indicated that Claudin-1 is upregulated in colorectal (de Oliveira, de Oliveira, De Souza, & Morgado-Diaz, 2005), melanoma (Leotlela et al, 2007), and gastric cancer (Eftang et al, 2013) and can promote the epithelialmesenchymal transition (EMT; Stebbing, Filipović, & Giamas, 2013).…”