Caday C G, Klagsbrun M, Fanning P J, Mirzabegian A, Finklestein S P
CNS Growth Factor Research Laboratory, Massachusetts General Hospital, Boston 02114.
Brain Res Dev Brain Res. 1990 Mar 1;52(1-2):241-6. doi: 10.1016/0165-3806(90)90240-y.
Acidic and basic fibroblast growth factors (FGF) are polypeptides with potent multipotential trophic effects on central nervous system (CNS) glia, endothelial cells, and neurons. These factors are characterized by strong binding to heparin, and are commonly assayed by their mitogenic activity on Balb/c 3T3 cells in vitro. We found a marked (ca. 13-fold) increase in Balb/c 3T3 mitogenic activity in the developing rat brain from the embryonic stage to the third postnatal week. High levels were sustained in the mature brain. Most of the mitogenic activity from rat brain bound strongly to heparin-affinity columns, and was eluted at positions characteristic of acidic FGF (aFGF) and basic FGF (bFGF). The presence of aFGF and bFGF in eluted peaks was confirmed by immunoblotting techniques using specific anti-FGF sera. Heparin-affinity high performance liquid chromatography (HPLC) showed a proportionately greater increase in levels of aFGF than bFGF between the tenth and fortieth postnatal days. Increases in FGF levels during late embryonic and early postnatal stages of brain development may play an important role in the glial and capillary proliferation, as well as in the neuronal outgrowth and synapse formation that is occurring during this time. The differential rates of accumulation of aFGF vs bFGF suggest different physiological roles for these factors in the developing brain.
酸性和碱性成纤维细胞生长因子（FGF）是对中枢神经系统（CNS）神经胶质细胞、内皮细胞和神经元具有强大多潜能营养作用的多肽。这些因子的特点是与肝素紧密结合，通常通过它们在体外对Balb/c 3T3细胞的促有丝分裂活性来测定。我们发现，从胚胎期到出生后第三周，发育中的大鼠脑内Balb/c 3T3细胞促有丝分裂活性显著增加（约13倍）。在成熟脑中该活性维持在较高水平。大鼠脑内的大部分促有丝分裂活性与肝素亲和柱紧密结合，并在酸性FGF（aFGF）和碱性FGF（bFGF）的特征位置被洗脱。使用特异性抗FGF血清的免疫印迹技术证实了洗脱峰中存在aFGF和bFGF。肝素亲和高效液相色谱（HPLC）显示，在出生后第10天到第40天之间，aFGF水平的增加比例大于bFGF。在胚胎后期和出生后早期脑发育阶段FGF水平的增加，可能在神经胶质细胞和毛细血管增殖以及此时发生的神经元生长和突触形成中起重要作用。aFGF与bFGF积累速率的差异表明这些因子在发育中的脑中具有不同的生理作用。
