Tada Toyohiro, Ito Jin-ichi, Asai Michiyo, Yokoyama Shinji
Department of Pathology, Nagoya City University School of Nursing, Nagoya 467-8601, Japan.
Neurochem Int. 2004 Jul;45(1):23-30. doi: 10.1016/j.neuint.2004.01.002.
We recently reported that fibroblast growth factor 1 (FGF-1) upregulates apolipoprotein E (apoE) synthesis and its secretion as high density lipoprotein (HDL) in cultured astrocytes potentially by an autocrine or paracrine mechanism [Biochim. Biopys. Acta 1589 (2002) 261]. In order to examine pathophysiological relevance of this reaction, we studied association of the production of FGF-1 and apoE in the post-injury mouse brain. After the spot-injury of the brain by liquid nitrogen, the surface size of the wound shrunk more rapidly in the C57BL/6 wild-type mice than the apoE-knock out C57BL/6 mice. Immunohistochemical analysis of the lesions revealed that production of FGF-1 was identified in the reactive astrocytes by the day 2 after the injury in both types of mouse, prior to the production of apoE confirmed by the day 4 in the wild-type. These findings were consistent with our in-vitro observations and hypothesis that FGF-1 upregulates apoE synthesis and subsequently HDL production in the reactive astrocytes by an autocrine or paracrine manner. FGF-1 thus would exert its effect after the CNS damage through apoE secretion.
我们最近报道，成纤维细胞生长因子1（FGF-1）可能通过自分泌或旁分泌机制，上调培养的星形胶质细胞中载脂蛋白E（apoE）的合成及其作为高密度脂蛋白（HDL）的分泌[《生物化学与生物物理学学报》1589（2002）261]。为了研究这种反应的病理生理相关性，我们研究了损伤后小鼠脑中FGF-1和apoE产生之间的关联。在用液氮对脑进行点状损伤后，C57BL/6野生型小鼠伤口的表面尺寸比apoE基因敲除的C57BL/6小鼠缩小得更快。对损伤部位的免疫组织化学分析显示，在两种类型的小鼠中，损伤后第2天在反应性星形胶质细胞中检测到FGF-1的产生，而野生型小鼠在第4天才确认有apoE的产生。这些发现与我们的体外观察结果和假说一致，即FGF-1通过自分泌或旁分泌方式上调反应性星形胶质细胞中apoE的合成，随后上调HDL的产生。因此，FGF-1可能在中枢神经系统损伤后通过apoE的分泌发挥作用。
