Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo

Abstract

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 transcriptasepolymerase 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.