Giordano S, Sherman L, Lyman W, Morrison R
R. S. Dow Neurological Sciences Institute and Comprehensive Cancer Center, Portland, Oregon 97209.
Dev Biol. 1992 Aug;152(2):293-303. doi: 10.1016/0012-1606(92)90136-5.
Basic fibroblast growth factor (bFGF) is a heparin-binding protein implicated in the differentiation, proliferation, and maintenance of cells in the central nervous system (CNS). It is not clear how bFGF achieves this multiplicity of effects. Multiple molecular weight forms of bFGF have recently been identified, however, and each form may have distinct activities during CNS development. We have examined the pattern of bFGF expression during CNS development using protein immunoblot and RNA blot analyses. RNA blot analysis detected a major bFGF transcript of 3.7 kb in embryonic and adult rat brain; however, this message decreased in abundance during development. Three bFGF protein forms were identified on immunoblots of adult rat brain extract with approximate molecular weights of 18, 21, and 22 kDa. Embryonic rat brain extracts also contained the 18- and 21-kDa bFGF protein forms, but lacked the 22-kDa form. Expression of the 22-kDa form was first detected in the neonate and then steadily increased to adult levels by 1 month of age. Immunoblots of adult human brain extracts also showed the presence of three bFGF protein forms with approximate molecular weights of 18, 22, and 24 kDa. In human second trimester fetal brain extracts, only the 18-kDa bFGF protein was detected. Comparison of bFGF proteins in developing rat spinal cord, cerebellum, and cortex demonstrated that distinct patterns of bFGF protein forms exist in different regions of the CNS. Therefore, the expression of individual bFGF protein forms is regulated in the CNS with regard to both developmental stage and location. These data support the idea that different forms of bFGF may be associated with specific developmental events during the maturation and organization of the nervous system.
碱性成纤维细胞生长因子(bFGF)是一种肝素结合蛋白,与中枢神经系统(CNS)中细胞的分化、增殖和维持有关。目前尚不清楚bFGF是如何实现这种多种效应的。然而,最近已鉴定出多种分子量形式的bFGF,并且每种形式在CNS发育过程中可能具有不同的活性。我们使用蛋白质免疫印迹和RNA印迹分析研究了CNS发育过程中bFGF的表达模式。RNA印迹分析在胚胎和成年大鼠脑中检测到一种3.7 kb的主要bFGF转录本;然而,这条信息在发育过程中丰度下降。在成年大鼠脑提取物的免疫印迹上鉴定出三种bFGF蛋白形式,其近似分子量分别为18、21和22 kDa。胚胎大鼠脑提取物也含有18 kDa和21 kDa的bFGF蛋白形式,但缺乏22 kDa的形式。22 kDa形式的表达首先在新生儿中检测到,然后在1月龄时稳步增加至成年水平。成年人类脑提取物的免疫印迹也显示存在三种bFGF蛋白形式,其近似分子量分别为18、22和24 kDa。在人类孕中期胎儿脑提取物中,仅检测到18 kDa的bFGF蛋白。对发育中的大鼠脊髓、小脑和皮质中的bFGF蛋白进行比较表明,CNS的不同区域存在bFGF蛋白形式的不同模式。因此,在CNS中,个体bFGF蛋白形式的表达在发育阶段和位置方面均受到调节。这些数据支持这样一种观点,即不同形式的bFGF可能与神经系统成熟和组织过程中的特定发育事件相关。