The role and mechanism of tight junctions in the regulation of salivary gland secretion

Abstract

Tight junctions (TJs) are cell–cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic‐stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4‐related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.

Molecular mechanisms of saliva secretion and hyposecretion

“…Occludin-deleted mice have been reported to show a loss of cytoplasmic granules in the striated ducts but showed no significant difference in the acinar cells of the salivary gland [76]. The specific functions of other tight junction proteins in salivary glands using knockout mouse models have yet to be reported [73].…”

Claudin-10 Decrease in the Submandibular Gland Contributes to Xerostomia

“…Tight junctions (TJs) are cell–cell interactions that are widely expressed between neighboring epithelial/endothelial cells and strictly regulate material transport through the paracellular pathway in salivary glands (Baker 2010; Zhang et al 2013). Many studies have shown that an increased paracellular permeability is required for saliva secretion, whereas disruption of the TJ barrier leads to hyposecretion in diseases such as Sjögren syndrome and IgG4-related disease (Cong et al 2023). Claudin family members are the main backbone of transmembrane TJ strands, and they delicately control the size and charge of molecules that transport through the paracellular pathway relaying on the characteristics of their extracellular loops.…”

Artificial intelligence, cell therapies, acupuncture, and tight junctions: Advances in salivary research

“…Second is a review of cell‐based therapies to treat salivary dysfunctions due to radiotherapy and Sjögren's syndrome by I and colleagues from Nagasaki University, Japan (I et al., 2023). Third is a review of tight junctions in the regulation of salivary gland secretion by Cong and colleagues from Peking University (Cong et al., 2023). Fourth is an original paper on the use of acupuncture to treat Sjögren's syndrome patients and nonobese diabetic mice with Sjögren's‐like disease by Liu and colleagues from the China Academy of Chinese Medical Sciences (Liu et al., 2023).…”

“…Tight junctions function as selective gates controlling paracellular diffusion of ions and solutes across epithelial and endothelial cells, define apical and basolateral membrane domains (cell polarization), and affect cell signaling, gene expression, and cell proliferation (Zihni et al., 2016). In a comprehensive review, Cong and colleagues enrich our understanding of the cellular and molecular functions of epithelial and endothelial cells tight junctions in the regulation of salivary secretion during physiological and pathophysiological conditions such as those encountered in Sjögren's syndrome, diabetes mellitus, and radiotherapy (Cong et al., 2023).…”

“…Third is a review of tight junctions in the regulation of salivary gland secretion by Cong and colleagues from Peking University (Cong et al, 2023). Fourth is an original paper on the use of acupuncture to treat Sjögren's syndrome patients and nonobese diabetic mice with Sjögren's-like disease by Liu and colleagues from the China Academy of Chinese Medical Sciences (Liu et al, 2023).…”