Suppression of fibroblast growth factors 1 and 2 by antisense oligonucleotides in embryonic chick retinal cells in vitro inhibits neuronal differentiation and survival
Suppression of fibroblast growth factors 1 and 2 by antisense oligonucleotides in embryonic chick retinal cells in vitro inhibits neuronal differentiation and survival
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DOI：
10.1006/excr.1998.4048
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发表时间：
1998-05-25
影响因子：
3.7
通讯作者：
Jeanny, JC
中科院分区：
文献类型：
--
作者：
Désiré, L;Courtois, Y;Jeanny, JC
随着视网膜组织发生的进行，成纤维细胞生长因子（FGF）的表达显著增加，在成熟视网膜中达到最大值，并且主要在终末分化的视网膜神经元中。最近在体内的证据表明，外源性FGF的功能作为一个分化和生存因子的各种细胞类型，包括中枢神经系统神经元和内源性FGF可能执行类似的功能。我们已经研究了选择性和独立地抑制FGF 1或FGF 2的表达，在胚胎鸡视网膜细胞，在体外分化的反义寡核苷酸的后果。无论FGF1或FGF2表达被抑制，结果都是相同的：神经元感光细胞分化显著减少，程序性细胞死亡增加，但对细胞增殖没有影响。即使这两个相关因素促进对视网膜细胞的相同最终作用，即神经元分化和存活，它们的正常组合活性或水平似乎在实现这种作用中是重要的。用外源性FGF1或FGF2刺激用于增加FGF1和FGF2两者的内源性水平，并逆转FGF1或FGF2的反义阻断的作用。我们的数据表明，虽然其他来源的FGF存在于眼睛内，内源性FGF在分化视网膜神经元中的功能可能是刺激它们的分化和促进它们的存活。(C)北京：科学出版社.
As retinal histogenesis proceeds there is a pronounced increase in the expression of fibroblast growth factor (FGF), reaching its maximum in the mature retina and largely in terminal differentiated retinal neurons. Recent in vivo evidence suggests that exogenous FGF functions as a differentiation and survival factor for a wide variety of cell types including CNS neurons and that endogenous FGF may perform similar functions. We have examined the consequences of selectively and independently inhibiting FGF1 or FGF2 expression using antisense oligonucleotides in embryonic chick retinal cells, differentiating in vitro. Whether FGF1 or FGF2 expression was inhibited the results were the same: a marked reduction in neuronal photoreceptor cells differentiation, an increase in programmed cell death, but no effects on cell proliferation. Even although these two related factors promote the same final effect on retinal cells, namely, neuronal differentiation and survival, their normal combined activities or levels appear to be important in achieving this effect. Stimulation with either exogenous FGF1 or FGF2 served to increase endogenous levels of both FGF1 and FGF2 and reversed the effects of antisense blockade of either FGF1 or FGF2. Our data suggest that although other sources of FGF exist within the eye, the function of endogenous FGF in differentiating retinal neurons may be to stimulate their differentiation and promote their survival. (C) 1998 Academic Press.