Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery
Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery
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DOI：
10.1074/jbc.m209003200
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发表时间：
2002-11-29
影响因子：
4.8
通讯作者：
Verkman, AS
中科院分区：
文献类型：
--
作者：
Hara, M;Ma, TH;Verkman, AS
小鼠中表皮水/甘油转运蛋白水通道蛋白-3 (AQP3) 的缺失使浅表皮肤电导降低了 2 倍（Ma, T., Hara, M., Sougrat, R., Verbavatz, J. M., and Verkman, A. S. (2002) J. Biol. Chem. 277, 17147-17153），表明有缺陷角质层。 (SC) 水合作用。在这里，我们证明了无毛（SKH1）遗传背景下 AQP3 缺失小鼠的皮肤水合作用、弹性、屏障恢复和伤口愈合显着受损，并通过分析 SC 形态和成分来研究功能缺陷的原因。利用新型 (H2O)-H-3 分配方法，AQP3 缺失小鼠中 SC 含水量减少了约 50%。在 AQP3 缺失小鼠中，通过皮肤测量测量的皮肤弹性显着降低，弹性参数 Uf、Ue 和 Ur 降低了 50%。尽管基础皮肤屏障功能没有受损，但AQP3缺失导致屏障功能的恢复延迟了两倍，这是通过胶带剥离后经皮水分流失来测量的。另一种生物合成皮肤功能，即伤口愈合，也与 AQP3 缺失延迟两倍相似。通过电子显微镜观察，AQP3 缺失并不影响未受干扰的 SC 的结构。离子（Na+、K+、Ca2+、Mg2+）和小溶质（尿素、乳酸、葡萄糖）的 SC 含量不受 AQP3 缺失的影响，脂质和游离氨基酸的绝对量或分布也不受 AQP3 缺失的影响。然而，AQP3缺失导致SC和表皮中甘油含量显着降低（以nmol/mug蛋白计：SC中5.5+/-0.4对比2.3+/-0.7；表皮中0.037+/-0.007对比0.022+/-0.005），但真皮或血液中的甘油含量没有显着降低。这些结果确定了 AQP3 缺陷小鼠皮肤的水合、机械和生物合成缺陷。 AQP3 缺失小鼠表皮和 SC 甘油含量的选择性减少可能是这些缺陷的原因，为水通道蛋白进行生理上重要的甘油转运提供了第一个功能证据。
Deletion of the epidermal water/glycerol transporter aquaporin-3 (AQP3) in mice reduced superficial skin conductance by similar to2-fold (Ma, T., Hara, M., Sougrat, R., Verbavatz, J. M., and Verkman, A. S. (2002) J. Biol. Chem. 277, 17147-17153), suggesting defective stratum corneum. (SC) hydration. Here, we demonstrate significant impairment of skin hydration, elasticity, barrier recovery, and wound healing in AQP3 null mice in a hairless (SKH1) genetic background and investigate the cause of the functional defects by analysis of SC morphology and composition. Utilizing a novel (H2O)-H-3 distribution method, SC water content was reduced by similar to50% in AQP3 null mice. Skin elasticity measured by cutometry was significantly reduced in AQP3 null mice with similar to50% reductions in elasticity parameters Uf, Ue, and Ur. Although basal skin barrier function was not impaired, AQP3 deletion produced an similar to2-fold delay in recovery of barrier function as measured by transepidermal water loss after tape stripping. Another biosynthetic skin function, wound healing, was also similar to2-fold delayed by AQP3 deletion. By electron microscopy AQP3 deletion did not affect the structure of the unperturbed SC. The SC content of ions (Na+, K+, Ca2+, Mg2+) and small solutes (urea, lactic acid, glucose) was not affected by AQP3 deletion nor was the absolute amount or profile of lipids and free amino acids. However, AQP3 deletion produced significant reductions in glycerol content in SC and epidermis (in nmol/mug protein: 5.5 +/- 0.4 versus 2.3 +/- 0.7 in SC; 0.037 +/- 0.007 versus 0.022 +/- 0.005 in epidermis) but not in dermis or blood. These results establish hydration, mechanical, and biosynthetic defects in skin of AQP3-deficient mice. The selective reduction in epidermal and SC glycerol content in AQP3 null mice may account for these defects, providing the first functional evidence for physiologically important glycerol transport by an aquaporin.