c‐Jun N‐terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells

Abstract

Tricellulin (TRIC) is a tight junction protein at tricellular contacts where three epithelial cells meet, and it is required for the maintenance of the epithelial barrier. To investigate whether TRIC is regulated via a c-Jun N-terminal kinase (JNK) pathway, human pancreatic HPAC cells, highly expressed at tricellular contacts, were exposed to various stimuli such as the JNK activators anisomycin and 12-O-tetradecanoylphorbol 13-acetate (TPA), and the proinflammatory cytokines IL-1β, TNFα, and IL-1α. TRIC expression and the barrier function were moderated by treatment with the JNK activator anisomycin, and suppressed not only by inhibitors of JNK and PKC but also by siRNAs of TRIC. TRIC expression was induced by treatment with the PKC activator TPA and proinflammatory cytokines IL-1β, TNFα, and IL-1α, whereas the changes were inhibited by a JNK inhibitor. Furthermore, in normal human pancreatic duct epithelial cells using hTERT-transfected primary cultured cells, the responses of TRIC expression to the various stimuli were similar to those in HPAC cells. TRIC expression in tricellular tight junctions is strongly regulated together with the barrier function via the JNK transduction pathway. These findings suggest that JNK may be involved in the regulation of tricellular tight junctions including TRIC expression and the barrier function during normal remodeling of epithelial cells, and prevent disruption of the epithelial barrier in inflammation and other disorders in pancreatic duct epithelial cells.

A role for tricellulin in the regulation of gill epithelium permeability

“…In fishes, another member of the TAMP subfamily, occludin, has also been found in a broad array of tissues (7,10). In addition, broad TRIC expression in trout was comparable to reports in mammals (26,33,35,47,50), where it has been found in testis, small intestine, kidney, lung, liver, brain, inner ear, retina, epidermal cells, and pancreas. Furthermore, cytosolic TJ proteins such as zonula occludens 1 (ZO-1) also show broad and consistent expression patterns in fish tissues (8).…”

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

“…Enteritidis AvrA Inhibits Cellular JNK Activation-ZO-1 is regulated by the JNK signaling pathway (25,39,40). Using Western blotting, we found that JNK signaling was activated, as indicated by the marked increase in JNK phosphorylation, in Caco-2 BBE, HCT116, and SKCO15 cells following S. Enteritidis colonization (Fig.…”

The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

“…Gene silencing of tricellulin in epithelial cells has been shown to induce irregularities in cellular shape and disorganisation of F-actin fibers, owing to the inactivation of Cdc42 by tricellulin and accordingly impairment of junctional tension (74). Furthermore, in normal human pancreatic duct epithelial cells, the c-Jun N-terminal kinase (JNK) pathway has been found to regulate tricellulin expression at tricellular junctions in addition to epithelial barrier function (75). Interestingly, occludin silencing has been linked with tricellulin relocalisation to bicellular tight junctions, highlighting an important role for occludin in tricellular tight junction maintenance (71) despite the fact that occludin and tricellulin are not known to physically interact with each other (73).…”