Role of aquaporins in lung liquid physiology
Role of aquaporins in lung liquid physiology
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DOI：
10.1016/j.resp.2007.02.012
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发表时间：
2007-12-15
影响因子：
2.3
通讯作者：
Verkman, A. S.
中科院分区：
文献类型：
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作者：
Verkman, A. S.
水通道蛋白（AQPs）是一种小的、完整的膜蛋白，在渗透梯度的作用下促进水在细胞膜上的运输。在气道水化、肺泡液运输和粘膜下腺分泌过程中，水在肺外周和气道的上皮和内皮之间进行运输。几种AQPs在肺和气道中表达：AQP1在微血管内皮中表达，AQP3和AQP4在气道上皮中表达，AQP5在I型肺泡上皮细胞、粘膜下腺腺泡细胞和一部分气道上皮细胞中表达。缺乏AQPs的转基因敲除小鼠的表型分析已经确定了它们在肺和气道中的作用。AQP1和AQP5是渗透驱动水分在空域和毛细管间输运的主要途径；然而，新生儿和成人肺的肺泡液清除不受其缺失的影响，肺损伤实验模型中的肺液积聚也不受其影响。在气道中，虽然AQP3和AQP4促进渗透水运输，但它们的缺失并不影响气道水化、气道表面液体调节或液体吸收。与这些阴性结果相反，粘膜下腺AQP5的缺失使液体分泌减少了50%以上。与肾上皮和分泌上皮相比，肺中的液体运输明显缓慢，这可能是AQPs在肺和气道中缺乏功能意义的原因。最近肺外的数据表明AQPs参与细胞迁移和增殖，表明肺AQPs可能的新作用有待探索。(C) 2007 Elsevier B.V.版权所有
Aquaporins (AQPs) are small, integral membrane proteins that facilitate water transport across cell membranes in response to osmotic gradients. Water transport across epithelia and endothelia in the peripheral lung and airways occurs during airway hydration, alveolar fluid transport and submucosal gland secretion. Several AQPs are expressed in the lung and airways: AQP1 in microvascular endothelia, AQP3 and AQP4 in airway epithelia, and AQP5 in type I alveolar epithelial cells, submucosal gland acini, and a subset of airway epithelial cells. Phenotype analysis of transgenic knockout mice lacking AQPs has defined their roles in the lung and airways. AQP1 and AQP5 provide the principal route for osmotically driven water transport between airspace and capillary compartments; however, alveolar fluid clearance in the neonatal and adult lung is not affected by their deletion, nor is lung fluid accumulation in experimental models of lung injury. In the airways, though AQP3 and AQP4 facilitate osmotic water transport, their deletion does not impair airway hydration, regulation of airway surface liquid, or fluid absorption. In contrast to these negative findings, AQP5 deletion in submucosal glands reduced fluid secretion by >50%. The substantially slower fluid transport in the lung compared to renal and secretory epithelia probably accounts for the lack of functional significance of AQPs in the lung and airways. Recent data outside of the lung implicating the involvement of AQPs in cell migration and proliferation suggests possible new roles for lung AQPs to be explored. (C) 2007 Elsevier B.V. All rights reserved.