Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation

Abstract

The intestinal epithelium forms a highly dynamic and selective barrier that controls absorption of fluid and solutes while restricting pathogen access to underlying tissues. Barrier properties are achieved by intercellular junctions that include an apical tight junction (TJ) and subjacent adherens junction and desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells to control paracellular fluid and ion movement. In addition to regulation of barrier function, claudin family members control epithelial homeostasis and are expressed in a spatiotemporal manner in the intestinal and crypt-luminal axis. This delicate balance of physiologic differential claudin protein expression is altered during mucosal inflammation. Inflammatory mediators influence transcriptional regulation, as well as endocytic trafficking, targeting, and retention of claudins in the TJ. Increased expression of intestinal epithelial claudin-1, -2, and -18, with downregulation of claudin-3, -4, -5, -7, -8, and -12, has been observed in intestinal inflammatory disorders. Such changes in claudin proteins modify the epithelial barrier function in addition to influencing epithelial and mucosal homeostasis. An improved understanding of the regulatory mechanisms that control epithelial claudin proteins will provide strategies to strengthen the epithelial barrier function and restore mucosal homeostasis in inflammatory disorders.

The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium

“…Additionally, its protein expression was detected throughout the crypt-villus axis of human small intestines but was only detected in undifferentiated crypt cells of human colonic tissue [36]. Other claudins follow suit regarding crypt-luminal axis expression with some pore-forming claudins (-2, -10, -13, -15) being restricted to the intestinal crypt base in murine tissue while other sealing claudins (-3, -4, -7, -8) are expressed in luminal epithelial cells [37][38][39][40].…”

Lactobacillus pentosus S-PT84 and Rubus suavissimus leaf extract suppress lipopolysaccharide-induced gut permeability and egg allergen uptake

“…Thus, it was suggested that both the S-PT84 and RSLE contributed in maintaining the gut barrier integrity at the presence of LPS. Craudin-4 is dominantly expressed in the ileum and belongs as sealing Cld (Garcia-Hernandez et al 2017). It was suggested that the decrease of Cld-4 by LPS was related to the elevated intestinal permeability.…”

“…It has been reported that Cld-2 is highly expressed in leaky epithelia of gastrointestinal inflammation (Luettig et al 2015). Craudin-2 forms channel for cation and water within TJs (Garcia-Hernandez et al 2017). Although Cld-2 cannot transport uncharged oligomers such as D-mannitol and LPS, increase of Cld-2 in tight junction could affect the pattern of tight junction strand, resulting in barrier disturbance (Luettig et al 2015;Liu et al 2013).…”

“…The TJs in the intestinal surface also acts as a protective barrier for pathogens, toxins, and allergens. Proteins (claudins (Cld), ZO proteins, occludin, and tricellulin) present in the TJs have dynamic structure and actively remodeled during a variety of conditions of the intestine (Furuse 2010;Garcia-Hernandez et al 2017). are detected in mouse intestine using reverse transcriptase PCR.…”

Microarray Analysis of Differentially Expressed Profiles of Circular RNAs in a Mouse Model of Intestinal Ischemia/Reperfusion Injury with and Without Ischemic Postconditioning

“…As circRNAs may regulate the transcription of their parent genes [32], those circRNAs described above may play roles in intestinal I/R injury The data from the mRNA microarray were also encouraging. Of the top 10 dysregulated mRNAs modulated by intestinal I/R injury, Cldn3 (claudin-3) had the highest fold change among the downregulated mRNAs and was previously identified as a key tight junction protein that helps establish the paracellular barrier of the intestinal epithelia [33]. The significantly decreased gene expression of Cldn3 and Cldn15 indicated a defect in intestinal epithelial barrier function after I/R injury [34,35], while decreased Gpx2 expression implied a low intracellular antioxidant level in intestinal I/R progression, as suggested by previous studies [36].…”