Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion

Although salivary glands are highly vascularized, the microvascular endothelial barrier has only recently emerged as a pivotal determinant of glandular homeostasis and disease. This review synthesizes current understanding of the salivary gland endothelial barrier, with particular emphasis on the regulation of tight junctions (TJs). Structurally, the barrier comprises endothelial cells interconnected by TJs and adherens junctions, supported by a basement membrane and pericytes. Among TJ components, claudin-5 serves as a key endothelial-specific regulator of paracellular permeability, and is dynamically modulated by biochemical and mechanical stimuli during saliva secretion. Cholinergic, adrenergic, and neuropeptide signaling pathways coordinate to fine-tune endothelial permeability to meet the fluctuating secretory demands. Conversely, under pathological conditions, such as Sjögren's syndrome, radiation-induced injury, diabetes mellitus, fibrotic diseases, and salivary gland tumors, the integrity of the endothelial TJ complex is impaired. These pathologies are characterized by aberrant TJ expression, mislocalization, and signaling-mediated junctional disassembly, which trigger vascular leakage and immune cell infiltration-two key processes that act as primary drivers of glandular dysfunction. Collectively, these findings enrich our understanding of the microvascular mechanisms that link endothelial barrier function to salivation, and highlight that the restoration of junctional integrity is a promising therapeutic strategy for salivary gland diseases.