Box 1 Two distinct pathways across epithelial/endothelial cellular sheets
There are two pathways through which materials cross epithelial/endothelial cellular sheets: the transcellular and paracellular pathways. The transepithelial resistance of epithelia from different tissues varies by two orders of magnitude, which is thought largely to reflect variations in the permeability of TJs (91). The permeability of TJs shows the charge and size selectivity. Ions transport across TJs is cation selective (92). Anion-selective transport was found in a few exceptions such as the rabbit colon and frog skin92. Non-charged materials such as water and sucrose also move across TJs (4,5). Under various physiological conditions, material transport across TJs occurs in a regulated fashion, and its regulation in certain states may be coupled to transcellular transport (91,93). For example, during absorption of glucose from the intestine, a large fraction of glucose may actually occur be transported across TJs, particularly when luminal glucose concentrations are far above that at which the Na+-glucose cotransporter at apical membranes is saturated (91). Activation of Na+-glucose cotransporter is thought to alter the structure and function of TJs, but the molecular mechanism underlying this coupling remains unclear.