Tradtrantip Lukmanee, Tajima Masato, Li Lihua, Verkman A S
Department of Medicine, University of California, San Francisco, CA 94143-0521, USA.
J Med Invest. 2009;56 Suppl(Suppl):179-84. doi: 10.2152/jmi.56.179.
Aquaporins (AQPs) are membrane water channels that are involved in a diverse set of functions in mammalian physiology including epithelial fluid transport, brain water balance, cell migration, cell proliferation, neuroexcitation, fat metabolism, epidermal hydration, and others. Phenotype analysis of knockout mice has demonstrated an important role for AQPs in transepithelial fluid transport in kidney tubules, salivary and airway submucosal glands, choroid plexus and ciliary epithelium. The physiological functions of these epithelia, such as absorption of glomerular filtrate by proximal tubule and secretion of saliva by salivary gland, involve rapid transcellular water transport across epithelial cell barriers. Studies in knockout mice have also provided evidence that AQPs are not physiologically important in some epithelia where they are expressed, including lacrimal gland, sweat gland, gallbladder, alveoli and airways. Rates of transepithelial fluid transport per unit membrane surface area in these epithelia are substantially lower than transepithelial fluid transport rates in proximal tubule and salivary gland. Pharmacological inhibition of AQP water permeability in epithelia, with consequent reduced fluid transport, offers potential therapy for human diseases involving water imbalance such as congestive heart failure, hypertension and glaucoma.
水通道蛋白（AQPs）是细胞膜上的水通道，参与哺乳动物生理学中的多种功能，包括上皮液体运输、脑水平衡、细胞迁移、细胞增殖、神经兴奋、脂肪代谢、表皮水合作用等。基因敲除小鼠的表型分析表明，水通道蛋白在肾小管、唾液腺和气道黏膜下腺、脉络丛和睫状体上皮的跨上皮液体运输中起重要作用。这些上皮组织的生理功能，如近端小管对肾小球滤液的吸收和唾液腺对唾液的分泌，涉及跨上皮细胞屏障的快速跨细胞水运输。对基因敲除小鼠的研究也提供了证据，表明水通道蛋白在一些表达它们的上皮组织中并非生理上重要，包括泪腺、汗腺、胆囊、肺泡和气道。这些上皮组织中单位膜表面积的跨上皮液体运输速率远低于近端小管和唾液腺中的跨上皮液体运输速率。通过药物抑制上皮组织中水通道蛋白的水通透性，从而降低液体运输，为涉及水失衡的人类疾病如充血性心力衰竭、高血压和青光眼提供了潜在的治疗方法。
