Ma Tonghui, Hara Mariko, Sougrat Rachid, Verbavatz Jean-Marc, Verkman A S
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
J Biol Chem. 2002 May 10;277(19):17147-53. doi: 10.1074/jbc.M200925200. Epub 2002 Mar 5.
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 wild-type 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 (microS), p < 0.001), as well as in a CD1 genetic background (209 +/- 21 versus 469 +/- 11 microS). Reduced SC hydration was seen from 3 days after birth. SC hydration in hairless wild-type and AQP3 null mice was reduced to comparable levels (90-100 microS) 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 microS). 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.
表皮的水和溶质转运特性被认为是皮肤水分含量和屏障特性的重要决定因素。通过免疫荧光和免疫金电子显微镜发现，水/小溶质转运蛋白水通道蛋白3（AQP3）在小鼠皮肤表皮角质形成细胞的质膜上表达。我们通过对在无毛SKH1遗传背景下产生的野生型和AQP3基因敲除小鼠进行比较测量，研究了AQP3在角质层（SC）水合作用中的作用。无毛AQP3基因敲除小鼠围产期存活、生长和血清化学指标正常，但由于尿液浓缩能力缺陷而多尿。AQP3缺失导致表皮的渗透水通透性降低4倍以上，甘油通透性降低2倍以上。AQP3缺失对表皮、真皮和SC的厚度及形态没有明显影响。表面电导测量显示，在无毛遗传背景下，AQP3基因敲除小鼠的SC含水量显著降低（165±10对269±12微西门子（μS），p<0.001），在CD1遗传背景下也是如此（209±21对469±11μS）。出生后3天就出现了SC水合作用降低的情况。无毛野生型和AQP3基因敲除小鼠在暴露于干燥大气24小时后，SC水合作用降低到相当水平（90-100μS），但当通过封闭或暴露于潮湿大气防止表面蒸发时，差异增大（179±13对441±34μS）。连续胶带剥离后的电导测量表明，AQP3基因敲除小鼠整个SC的含水量降低。水吸附-解吸实验表明，AQP3基因敲除小鼠的SC持水能力降低。AQP3基因敲除小鼠皮肤水合作用受损为AQP3参与皮肤生理功能提供了首个功能证据。因此，调节AQP3的表达或功能可能会改变皮肤疾病中表皮的水分含量和水分流失。
