Impaired Stratum Corneum Hydration in Mice Lacking Epidermal Water Channel Aquaporin-3

Abstract

The water and solute transporting properties of the epidermis have been proposed to be important determinants of skin moisture content and barrier properties. The water/small solute-transporting protein aquaporin-3 (AQP3) was found by immunofluorescence and immunogold electron microscopy to be expressed at the plasma membrane of epidermal keratinocytes in mouse skin. We studied the role of AQP3 in stratum corneum (SC) hydration by comparative measurements in wildtype and AQP3 null mice generated in a hairless SKH1 genetic background. The hairless AQP3 null mice had normal perinatal survival, growth, and serum chemistries but were polyuric because of defective urinary concentrating ability. AQP3 deletion resulted in a >4-fold reduced osmotic water permeability and >2-fold reduced glycerol permeability in epidermis. Epidermal, dermal, and SC thickness and morphology were not grossly affected by AQP3 deletion. Surface conductance measurements showed remarkably reduced SC water content in AQP3 null mice in the hairless genetic background (165 ؎ 10 versus 269 ؎ 12 microsiemens (S), p < 0.001), as well as in a CD1 genetic background (209 ؎ 21 versus 469 ؎ 11 S). Reduced SC hydration was seen from 3 days after birth. SC hydration in hairless wildtype and AQP3 null mice was reduced to comparable levels (90 -100 S) after a 24-h exposure to a dry atmosphere, but the difference was increased when surface evaporation was prevented by occlusion or exposure to a humidified atmosphere (179 ؎ 13 versus 441 ؎ 34 S). Conductance measurements after serial tape stripping suggested reduced water content throughout the SC in AQP3 null mice. Water sorption-desorption experiments indicated reduced water holding capacity in the SC of AQP3 null mice. The impaired skin hydration in AQP3 null mice provides the first functional evidence for the involvement of AQP3 in skin physiology. Modulation of AQP3 expression or function may thus alter epidermal moisture content and water loss in skin diseases.The water content of the stratum corneum is an important determinant of the appearance, physical properties, and barrier function of the skin (1-3). The stratum corneum, the most superficial layer of skin, consists of layers of flattened corneocytes (dead epidermal cells) embedded in a lipid-rich matrix containing specialized proteins and lipids (4). Abnormalities of stratum corneum hydration are seen in a variety of hereditary and acquired skin diseases such as atopic dermatitis (5), eczema (6), psoriasis (7), senile xerosis (8), and hereditary ichthyosis (9). Hydration of the stratum corneum could in principle be determined by a number of factors including the concentration of water-retaining osmolytes, the water and solute transporting properties of the underlying layers of viable epidermal keratinocytes, and the barrier properties of the stratum corneum. There is evidence for a high concentration of solutes (Na ϩ , K ϩ , and Cl Ϫ ) and a low concentration of water (13-35%, Ref. 10) in the superficial stratum corneum, producing in the steady-st...

Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue

“…AQP3 is expressed in the basal layer of keratinocytes and is thought to transport glycerol to the epidermis in response to dermal-to-epidermal gradient. Previous studies on Aqp3 null mice showed reduced glycerol content in the epidermis and impaired skin elasticity, barrier recovery, and wound healing, but normal serum glycerol concentrations (34)(35)(36). On the other hand, AQP9 is expressed in the liver and coordinately regulated with AQP7 in response to fasting͞feeding (15).…”

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“…In mammalian skin, AQP3 is expressed strongly in plasma membranes of the basal epidermal cell layer. Phenotype analysis of AQP3 null mice showed dry skin and delayed barrier recovery after removal of the stratum corneum [20][21][22]. These defects were attributed to the absence of AQP3-facilitated glycerol transport, resulting in reduced stratum corneum and epidermal cell glycerol content [20,21].…”

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“…1E). Mice lacking AQP3, which is normally expressed in the basal layer of keratinocytes in epidermis, manifest reduced stratum corneum hydration and skin elasticity, and impaired stratum corneum biosynthesis and wound healing (Ma et al, 2002). The mechanism responsible for the skin phenotype in AQP3 deficiency involves reduced epidermal cell skin glycerol permeability, resulting in reduced glycerol content in the stratum corneum and epidermis (Hara and Verkman, 2003).…”