Heterogenous Gene Expression of Bicellular and Tricellular Tight Junction-Sealing Components in the Human Intestinal Tract

• Published in: Biological & pharmaceutical bulletin 2024/06/27, Vol.47(6), pp.1209-1217
• Main Authors: Tachibana, Keisuke, Bai, Lin, Sugimura, Sayaka, Fujioka, Hijiri, Kishimoto, Wataru, Mizuguchi, Hiroyuki, Nakase, Hiroshi, Kondoh, Masuo
• Format: Article
• Language: English
• Subjects: Adult; Aged; angulin; Biopsy; claudin; Claudins - genetics; Claudins - metabolism; Duodenum; Enhancers; Epithelial cells; Epithelium; Female; Gene Expression; human intestine; Humans; Ileum; Intestinal Mucosa - metabolism; Jejunum; Large intestine; Male; MARVEL Domain Containing 2 Protein - genetics; MARVEL Domain Containing 2 Protein - metabolism; Middle Aged; Occludin - genetics; Occludin - metabolism; Oral administration; permeation enhancer; Rectum; RNA, Messenger - genetics; RNA, Messenger - metabolism; Small intestine; tight junction; Tight junctions; Tight Junctions - metabolism
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b23-00927

A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.