2017/05/10 by Vicky Garcia‐Hernandez, Vicky García‐Hernández, Miguel Quirós +2 · 2 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Barrier Structure and Function Studies #Gut microbiota and health #Neurological Disease Mechanisms and Treatments
paper · doi:10.1111/nyas.13360
openalex publication_date 2017/05/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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 junctions 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 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.