Role of tight junctions in signal transduction: an update.

Tight junctions (TJs), which are the most apically located of the intercellular junctional complexes, have a barrier function and a fence function. Recent studies show that they also participate in signal transduction mechanisms. TJs are modulated by intracellular signaling pathways including protein kinase C, mitogen-activated protein kinase, and NF-ϰB, to affect the epithelial barrier function in response to diverse stimuli. TJs are also regulated by various cytokines, growth factors, and hormones via signaling pathways. To investigate the regulation of TJ molecules via signaling pathways in human epithelial cells under normal and pathological conditions, we established a novel model of human telomerase reverse transcriptase-transfected human epithelial cells. In this review, we describe the recent progress in our understanding of the role of TJs for signal transduction under normal conditions in upper airway epithelium, pancreatic duct epithelial cells, hepatocytes, and endometrial epithelial cells, and in pathological conditions including cancer and infection.