Mechanism and treatment prospects of aquaporins 3 and 5 in Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disease, characterized by the infiltration of exocrine glands (especially salivary and lacrimal glands) by a large number of lymphocytes, leading to the core clinical manifestations of dry mouth and dry eyes. Aquaporins (AQPs) are a key family of proteins that regulate the transmembrane transport of water molecules and are crucial for maintaining the normal secretory functions of exocrine glands. Recent studies have shown that specific AQP molecules, particularly the abnormal localization of AQP5 (such as intracellular mislocalization) in salivary and lacrimal gland cell membranes and the downregulation of AQP3 expression levels in some tissues, are directly related to impaired water transport functions. This functional impairment leads to a decrease in the secretory capacity of glandular cells, exacerbating the core symptoms of dry mouth and dry eyes. More importantly, the abnormal expression and localization of AQPs are not only a characteristic of SS pathophysiology but also may participate in or amplify the autoimmune damage to the glands. This review aims to summarize the specific roles of AQP3 and AQP5 in the development of SS, focusing on changes in expression and localization in affected tissues (salivary and lacrimal glands), related molecular regulatory mechanisms (such as the effects of inflammatory factors), evidence from animal models, and lead directly to glandular secretory dysfunction. These findings demonstrate the pivotal role of dysregulation in the expression and function of AQPs (particularly AQP3 and AQP5) in SS, which provides new ideas for designing new treatment strategies integrating "pathway-structure-function" with AQPs as the core target in the future.