736 Aquaporin-3 in hidradenitis suppurativa: A novel player in keratinocytes’ biology

The main aquaporin in the epidermis is aquaporin-3 (AQP3), a water, glycerol and hydrogen peroxide channel protein primarily expressed in proliferating and early differentiating keratinocytes; given its role in keratinocytes homeostasis and epidermal barrier formation, our aim is to study AQP3 in Hidradenitis Suppurativa (HS). By immunohistochemistry, AQP3 expression and localization were assessed in skin biopsies from lesional and unaffected regions of HS patients, compared with healthy skin. Variations of AQP3 levels (RT-PCR and Western blot) were investigated in human keratinocytes cells (HaCaT) wild type and knockout (KO) for the major two genes associated with HS, NCSTN (NC) and PSENEN (PS). We also explored the effect of glyceryl glucoside (GG) in promoting AQP3 levels and wound closure rate, provoked in a monolayer of HaCaT KO cells. Considerable alterations of AQP3 expression and localization were detected in the epidermis and hair follicles of HS lesional areas where AQP3 was almost absent in the basal layer and gradually increased until the top of the spinous layer. In HaCaT KO cells, we confirmed a significant decrease in both mRNA (p<0.01) and protein levels (p<0.01) if compared to WT cells, suggesting that a diminished AQP3 expression could be a hallmark of HS. Aimed at rescuing the decrease of AQP3 expression, we identified a compound, GG, able to increase mRNA (p<0.05) and protein levels (p<0.01) of AQP3, as well as to accelerate wound closure (NC:p<0.001 and PS:p<0.05) in HaCaT KO cells. Our findings suggest that AQP3 is a novel key player in keratinocytes' biology, thus a suitable drug target molecule; moreover, we identified a compound capable of increasing AQP3 expression and accelerating wound healing, suggesting a novel potential treatment.