RAGE-Mediated Signalling in Gynaecological Disorders: Review of Molecular Mechanisms and Therapeutic Perspectives

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is a unique multi-ligand member of the immunoglobulin superfamily that exists in both membrane-bound and soluble forms. Under physiological conditions, RAGE expression is low in most tissues; however, it is markedly upregulated in response to tissue injury, inflammation or metabolic stress. Ligand-induced activation of RAGE initiates complex intracellular signalling cascades that regulate inflammation, extracellular matrix remodelling, cell proliferation, survival and migration. METHODS: While the contribution of RAGE to diabetes and chronic inflammatory diseases is well established, its role in gynaecological disorders remains insufficiently characterized. RESULTS: This comprehensive review summarizes current evidence on the involvement of RAGE in the pathogenesis of benign gynaecological disorders, such as endometriosis and polycystic ovary syndrome (PCOS), pregnancy-related complications and malignant neoplasms of the female reproductive tract. CONCLUSIONS: It also discusses emerging therapeutic strategies aimed at targeting the RAGE pathway, highlighting their potential translational relevance in gynaecological practice.