Aquaporins in the Skin: Molecular Regulators of Hydration and Potential Targets for Cosmetic Applications

Skin hydration is fundamental for maintaining epidermal barrier integrity and overall skin homeostasis. Beyond traditional moisturizing agents, recent research has highlighted the role of aquaporins (AQPs), transmembrane water channels, in regulating epidermal hydration, barrier function, and cellular signalling. Among them, aquaporin-3 (AQP3), predominantly expressed in keratinocytes, has attracted particular attention due to its involvement in water and glycerol transport. Dysregulation of AQP expression has been associated with impaired barrier function, inflammatory skin disorders, and ageing. Growing evidence suggests that specific cosmetic ingredients and bioactive compounds, including glycerol, glyceryl glucoside, isosorbide dicaprylate, urea, retinoids, bakuchiol, peptides, plant extracts, and bacterial ferments, can modulate AQP3 expression, thereby improving skin hydration and resilience. Despite promising in vitro data, clinical evidence remains limited, mainly due to methodological and ethical constraints associated with assessing aquaporin expression in vivo. Nonetheless, aquaporins represent promising molecular targets for innovative cosmetic strategies aimed at enhancing hydration, promoting regeneration, and counteracting photoageing. Furthermore, AQP modulation may improve dermal delivery of active substances, providing new perspectives for advanced skincare formulation design. While the available evidence supports their cosmetic potential, emerging discussions on the safety of long-term AQP upregulation highlight the need for continued research and careful evaluation of such ingredients. Future studies should focus on elucidating the molecular mechanisms underlying AQP regulation and validating these findings in human clinical models.