Giordano M J, Mahadeo D K, He Y Y, Geist R T, Hsu C, Gutmann D H
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci Res. 1996 Jan 15;43(2):246-53. doi: 10.1002/(SICI)1097-4547(19960115)43:2<246::AID-JNR12>3.0.CO;2-4.
Tumor suppressor genes encode proteins involved in growth regulation in differentiating and proliferating cells. Previous work from our laboratory has demonstrated that the neurofibromatosis 1 (NF1) tumor suppressor gene is dramatically upregulated in astrocytes stimulated with dibutyryl cyclic AMP and proinflammatory cytokines. To explore the possibility that the NF1 gene product, neurofibromin, plays a role in the reactive gliosis seen in response to cerebral ischemia, expression of NF1 was examined in both focal and global models of rat cerebral ischemia. In this report, we demonstrate the increased expression of both neurofibromin and glial fibrillary acidic protein (GFAP) in astrocytes surrounding areas of focal ischemia. Similar increases in neurofibromin and GFAP immunoreactivity were also observed in reactive astrocytes in the hippocampal region in a global model of ischemia. These results suggest a novel role for the NF1 tumor suppressor gene in growth regulatory pathways involved in cellular remodeling and in response to injury.
肿瘤抑制基因编码参与分化和增殖细胞生长调控的蛋白质。我们实验室之前的研究表明，在二丁酰环磷腺苷和促炎细胞因子刺激的星形胶质细胞中，神经纤维瘤病1（NF1）肿瘤抑制基因显著上调。为了探究NF1基因产物神经纤维瘤蛋白在脑缺血后反应性胶质增生中发挥作用的可能性，我们在大鼠局灶性和全脑缺血模型中检测了NF1的表达。在本报告中，我们证明在局灶性缺血区域周围的星形胶质细胞中，神经纤维瘤蛋白和胶质纤维酸性蛋白（GFAP）的表达均增加。在全脑缺血模型的海马区反应性星形胶质细胞中，也观察到神经纤维瘤蛋白和GFAP免疫反应性有类似增加。这些结果表明，NF1肿瘤抑制基因在参与细胞重塑和损伤反应的生长调控途径中具有新的作用。
