Tight junctions in salivary epithelium

Abstract

Epithelial cell tight junctions (TJs) consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins) define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

Figure 1

Diagram representing acinar salivary secretion and TJ proteins. Activation of basolateral M3 muscarinic receptors by neurotransmitters (e.g., acetylcholine) initiates signaling cascades that stimulate apical Ca²⁺-dependent Cl⁻ channels. The stimulated efflux of Cl⁻ produces a transepithelial potential difference that drives Na⁺ and H₂O transport across the TJ. Alternatively, H₂O can reach the lumen by water channels. These events create a plasma-like primary secretion in the lumen. As the primary saliva passes through the ducts, Na⁺ and Cl⁻ are reabsorbed and K⁺ is secreted into the lumen. Inset (adapted from [55]) indicates the TJ proteins occludin, claudin, and JAM linked to the cytoskeleton via cytoplasmic ZO proteins. Clearly TJ structure varies depending on the cell function; the question is how combinations of TJ proteins define function in acinar and ductal cells.

Figure 2

Three-dimensional Par-C10 acinar-like spheres express TJ as markers of acinar differentiation. Protein expression was detected using immunofluorescence microscopy with goat antimouse occludin (a and d: red), rabbit anti-ZO-1 (b and d: green), followed by Hoechst nuclear stain (c and d: blue). Images were obtained and analyzed using a Carl Zeiss 510 confocal microscope. Sphere diameter taken at the widest point of the xy plane (I) is shown in μm. This model has been published [137].