MEK mediates in vitro neural transdifferentiation of the adult newt retinal pigment epithelium cells: Is FGF2 an induction factor?
MEK mediates in vitro neural transdifferentiation of the adult newt retinal pigment epithelium cells: Is FGF2 an induction factor?
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DOI：
10.1111/j.1600-0749.2007.00407.x
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发表时间：
2007-10-01
期刊：
影响因子：
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通讯作者：
Chiba, Chikafumi
中科院分区：
文献类型：
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作者：
Susaki, Kanako;Chiba, Chikafumi
成年蝾螈可以通过视网膜色素上皮(RPE)细胞的转分化来再生整个视网膜。然而，到目前为止，潜在的分子机制实际上仍然不清楚。另一方面，在胚胎/幼年脊椎动物中，由成纤维细胞生长因子-2(FGF2)激活的MEK[丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)]通路被认为参与了RPE向神经视网膜的转分化诱导。因此，我们利用培养系统研究了FGF2/MEK通路是否也参与了成年Newt RPE的转分化。在这里，我们表明成年的Newt RPE细胞可以切换到表达泛视网膜神经元(PRN)标记的神经细胞，例如乙酰化微管蛋白，并且MEK通路对于这一过程的诱导是必不可少的，而FGF2似乎不太可能是一个主要的诱导因素。此外，免疫组织化学显示，PRN标记物在含有视网膜前体细胞的1-3个细胞厚的再生视网膜出现之前不会表达。我们目前的结果表明，RPE细胞中MEK通路的激活可能参与了成年Newt视网膜再生的诱导过程，但如果是这样的话，我们必须采取补充机制，在转分化的初始过程中抑制MEK介导的PRN标记的错误表达。
Adult newts can regenerate their entire retinas through transdifferentiation of the retinal pigment epithelium (RPE) cells. As yet, however, underlying molecular mechanisms remain virtually unknown. On the other hand, in embryonic/larval vertebrates, an MEK [mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase] pathway activated by fibroblast growth factor-2 (FGF2) is suggested to be involved in the induction of transdifferentiation of the RPE into a neural retina. Therefore, we examined using culture systems whether the FGF2/MEK pathway is also involved in the adult newt RPE transdifferentiation. Here we show that the adult newt RPE cells can switch to neural cells expressing pan-retinal-neuron (PRN) markers such as acetylated tubulin, and that an MEK pathway is essential for the induction of this process, whereas FGF2 seems an unlikely primary induction factor. In addition, we show by immunohistochemistry that the PRN markers are not expressed until the 1-3 cells thick regenerating retina, which contains retinal progenitor cells, appears. Our current results suggest that the activation of an MEK pathway in RPE cells might be involved in the induction process of retinal regeneration in the adult newt, however if this is the case, we must assume complementary mechanisms that repress the MEK-mediated misexpression of PRN markers in the initial process of transdifferentiation.