Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action
Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action
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DOI：
10.1194/jlr.m400313-jlr200
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发表时间：
2005-04-01
影响因子：
6.5
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Ito, J;Nagayasu, Y;Yokoyama, S
在大鼠脑细胞的1个月原代培养后通过1周二次培养制备的星形胶质细胞（M/W细胞）比通过常规1周原代和1周二次培养制备的星形胶质细胞（W/W细胞）更多地合成和分泌载脂蛋白E（apoE）和胆固醇（Ueno，S.，J. Ito，Y. Nagayasu，T. Furukawa和S.横山2002.分泌到脑细胞培养基中的酸性成纤维细胞生长因子样因子上调大鼠星形胶质细胞中的apoE合成、HDL分泌和胆固醇代谢。生物化学生物Biophys. Acta. 1589：261-272）。M/W细胞也高表达成纤维细胞生长因子-1（FGF-1）mRNA。在两种细胞类型的细胞裂解物中鉴定出FGF-1，但M/W细胞将更多的FGF-1释放到培养基中。FGF-1和apoE的免疫组化染色显示，两者都定位于产生胶质细胞酸性蛋白的细胞。M/W细胞和FGF-1的条件培养基刺激W/W细胞释放apoE和胆固醇以产生更多的HDL。用山羊抗FGF-1抗体或肝素预处理耗尽M/W细胞条件培养基的刺激活性。培养基中抗FGF-1抗体的存在抑制了M/W细胞的apoE分泌。信号通路的差异抑制表明FGF-1通过PI 3 K/Akt通路的磷酸肌醇3-OH激酶刺激apoE合成。因此，星形胶质细胞释放FGF-1，其通过自分泌机制促进apoE-HDL的产生。这些结果与我们的体内观察一致，即在小鼠脑损伤后病变中星形胶质细胞在apoE增加之前产生FGF-1（Tada，T.，J. Ito，M. Asai和S.横山2004.成纤维细胞生长因子1在小鼠脑冷冻损伤后的星形胶质细胞中先于载脂蛋白E产生。
The astrocytes prepared by 1 week secondary culture after 1 month primary culture of rat brain cells (M/W cells) synthesized and secreted apolipoprotein E (apoE) and cholesterol more than the astrocytes prepared by conventional 1 week primary and 1 week secondary culture (W/W cells) (Ueno, S., J. Ito, Y. Nagayasu, T. Furukawa, and S. Yokoyama. 2002. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat astrocytes. Biochim. Biophys. Acta. 1589: 261-272). M/W cells also highly expressed fibroblast growth factor-1 (FGF-1) mRNA. FGF-1 was identified in the cell lysate of both cell types, but M/W cells released more of it into the medium. Immunostaining of FGF-1 and apoE revealed that both localized in the cells that produce glial fibrillary acidic protein. The conditioned media of M/W cells and FGF-1 stimulated W/W cells to release apoE and cholesterol to generate more HDL. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of M/W cell-conditioned medium. The presence of the anti-FGF-1 antibody in the medium suppressed apoE secretion by M/W cells. Differential inhibition of signaling pathways suggested that FGF-1 stimulates apoE synthesis via the phosphoinositide 3-OH kinase for PI3K/Akt pathway. Thus, astrocytes release FGF-1, which promotes apoE-HDL production by an autocrine mechanism. These results are consistent with our in vivo observation that astrocytes produce FGF-1 before the increase of apoE in the postinjury lesion of the mouse brain (Tada, T., J. Ito, M. Asai, and S. Yokoyama. 2004. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse brain.