Mucins in salivary gland development, regeneration, and disease

Mucins are large glycoproteins that can be grouped as membrane-bound or secreted. Membrane-bound mucins are essential contributors of the glycocalyx of mucosal surfaces where they play important biological roles in cell interactions and signaling. Secreted mucins are the main structural compo-nents of the mucus gel that covers the epithelium and contribute to the protection of the mucosa surface against allergens, debris, pathogens, drying, injury, and abrasive stress. MUC1 and MUC4 are plasma membrane-anchored mucins expressed in oral epithelium and salivary glands and are ubiquitously located in normal epithelia. MUC5B is the major secreted polymeric mucin present in human saliva and contains negatively charged glycans allowing the formation of a hydrophilic gel that hydrates and protects the oral epithelium. MUC7 is a secreted mucin present in saliva and has low viscoelasticity and high bacteria-agglutinating properties allowing clearance of microorganisms from the mouth by swallowing. The roles of mucins during development of salivary glands remain unknown. Few studies on mucin expression in human salivary glands' development and in murine models have been described to date. In sali-vary gland regeneration, mucins have been evaluated only as markers of functionality of the glandular acini after damage and/or regeneration ther-apy. Interestingly, changes in quality and quantity of salivary mucins have been observed in pathological conditions. Over-expression of specific mucins induced by pro-inflammatory cytokines and ectopic secretion of mucins to extracellular matrix (ECM) support evidence on a self-perpetuating mucin-cytokine signaling loop that may facilitate the maintenance of an inflammatory environment in chronic inflammatory diseases, such as Sjögren's syndrome (SS). However, the loss of a mucin member could predispose to infections and inflammatory diseases in a mucosa. A reduced sulfation of MUC5B has been observed in salivary glands of SS patients, aggravating their oral dryness. Tumoral cells of sali-vary glands express aberrant forms or high amounts of mucins, being pro-posed as markers of malignant transformation. In this chapter, we summarize the main structural and functional characteristics of salivary mucins, their expression during salivary gland development, and regeneration and alterations in mucin quantity and quality in pathological processes affecting the salivary gland.