Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo
Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo
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DOI：
10.1111/j.1440-1789.2007.00774.x
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发表时间：
2007-06-01
期刊：
影响因子：
2.3
通讯作者：
Konno, Hidehiko
中科院分区：
文献类型：
--
作者：
Satoh, Jun-ichi;Tabunoki, Hiroko;Konno, Hidehiko
水通道蛋白(Aquaporins，AQP)是一个进化保守的完整膜水转运蛋白家族。以前的研究表明，AQP1仅在脉络丛上皮细胞中表达，而AQP4在生理条件下定位于中枢神经系统(CNS)中星形胶质细胞的血管足。为探讨AQP在星形胶质细胞增生症相关神经系统疾病中的作用，我们研究了AQP1和AQP4在培养的人星形胶质细胞及多发性硬化(MS)、脑梗塞和对照组脑组织中的表达。通过逆转录聚合酶链式反应和免疫印迹分析，培养的人星形胶质细胞同时表达AQP1和AQP4的mRNA和蛋白，其中AQP4的水平在干扰素-伽玛作用下升高，但不受肿瘤坏死因子-α和白介素1-β的影响，而AQP1的水平不受所研究的任何细胞因子的影响。免疫印迹分析显示，MS患者和非MS患者脑组织匀浆中均检测到AQP1和AQP4蛋白，二者与胶质纤维酸性蛋白表达水平呈正相关。免疫组织化学显示，MS和脑缺血区血管周围有高度分支突起的星形胶质细胞和胶质瘢痕呈强阳性表达，巨噬细胞、神经元和少突胶质细胞胞体均不表达AQP1和AQP4。这些免疫组织化学结果表明，AQP4和AQP1在MS和以星形胶质细胞为主的缺血性脑损伤中表达增强，提示星形胶质细胞AQP在病理条件下维持中枢神经系统水平衡中起关键作用。
Aquaporins (AQP) constitute an evolutionarily conserved family of integral membrane water transport channel proteins. Previous studies indicate that AQP1 is expressed exclusively in the choroid plexus epithelium, while AQP4 is localized on the vascular foot of astrocytes in the central nervous system (CNS) under physiological conditions. To investigate a role of AQP in the pathophysiology of neurological diseases involving astrogliosis we studied the expression of AQP1 and AQP4 in cultured human astrocytes and brain tissues of multiple sclerosis (MS), cerebral infarction and control cases. By reverse transcriptase-polymerase chain reaction and western blot analysis, cultured human astrocytes co-expressed both AQP1 and AQP4 mRNA and proteins, where AQP4 levels were elevated by exposure to interferon-gamma but neither by tumor necrosis factor-alpha nor interleukin-1beta, whereas AQP1 levels were unaffected by any of the cytokines examined. By western blot analysis, AQP1 and AQP4 proteins were detected in the brain homogenates of the MS and non-MS cases, where both levels were correlated with those of glial fibrillary acid protein. By immunohistochemistry, astrocytes with highly branched processes surrounding blood vessels, along with glial scar, expressed intensely AQP1 and AQP4 in MS and ischemic brain lesions, whereas neither macrophages, neurons nor oligodendrocyte cell bodies were immunopositive. These immunohistochemical results indicate that the expression not only of AQP4 but also of AQP1 was enhanced in MS and ischemic brain lesions located predominantly in astrocytes, suggesting a pivotal role of astrocytic AQP in the maintenance of water homeostasis in the CNS under pathological conditions.