Department of Medicine, University of California, San Francisco, California 94143-0521, USA.
Annu Rev Med. 2012;63:303-16. doi: 10.1146/annurev-med-043010-193843.
The aquaporins are a family of membrane water channels, some of which also transport glycerol. They are involved in a wide range of physiological functions (including water/salt homeostasis, exocrine fluid secretion, and epidermal hydration) and human diseases (including glaucoma, cancer, epilepsy, and obesity). At the cellular level, aquaporin-mediated osmotic water transport across cell plasma membranes facilitates transepithelial fluid transport, cell migration, and neuroexcitation; aquaporin-mediated glycerol transport regulates cell proliferation, adipocyte metabolism, and epidermal water retention. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and congenital cataracts. The neuroinflammatory demyelinating disease neuromyelitis optica is marked by pathogenic autoantibodies against astrocyte water channel aquaporin-4. There remain broad opportunities for the development of aquaporin-based diagnostics and therapeutics. Disease-relevant aquaporin polymorphisms are beginning to be explored. There is great promise in the development of small-molecule aquaporin modulators for therapy of some types of refractory edema, brain swelling, neuroinflammation, glaucoma, epilepsy, cancer, pain, and obesity.
水通道蛋白是一类膜水通道，其中一些也可以转运甘油。它们参与了广泛的生理功能（包括水盐稳态、外分泌液分泌和表皮水合）和人类疾病（包括青光眼、癌症、癫痫和肥胖症）。在细胞水平上，水通道蛋白介导的细胞浆膜的渗透水转运促进了跨上皮液转运、细胞迁移和神经兴奋；水通道蛋白介导的甘油转运调节细胞增殖、脂肪细胞代谢和表皮水潴留。水通道蛋白功能丧失突变引起的遗传性疾病包括肾性尿崩症和先天性白内障。神经炎性脱髓鞘疾病视神经脊髓炎的特征是针对星形胶质细胞水通道 aquaporin-4 的致病性自身抗体。基于水通道蛋白的诊断和治疗方法仍有广泛的发展机会。与疾病相关的水通道蛋白多态性开始被探索。开发小分子水通道蛋白调节剂来治疗某些类型的难治性水肿、脑水肿、神经炎症、青光眼、癫痫、癌症、疼痛和肥胖症具有巨大的潜力。
