Duration of ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate
Duration of ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate
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DOI：
10.1111/j.1432-0436.2007.00167.x
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发表时间：
2007-09-01
期刊：
影响因子：
2.9
通讯作者：
Lovicu, Frank J.
中科院分区：
文献类型：
--
作者：
Iyengar, Laxmi;Wang, Qian;Lovicu, Frank J.
眼内环境对于透镜生长模式和极性的建立和维持是重要的。在眼睛的前房中，房水调节透镜上皮细胞增殖，而在后房中，玻璃体液调节透镜细胞分化成纤维细胞。已显示成纤维细胞生长因子（FGF）生长因子家族的成员诱导透镜上皮细胞进行细胞分裂并分化成纤维，低剂量的FGF能够诱导细胞增殖（但不诱导纤维分化），而诱导纤维分化需要较高剂量。这两种细胞事件已被证明是由MAPK/ERK 1/2信号通路调节。在本研究中，为了更好地了解ERK 1/2信号在调节透镜细胞增殖和分化中的作用，我们表征了不同剂量的FGF诱导的ERK 1/2信号特征，并将其与不同眼部介质诱导的ERK 1/2信号特征进行了比较。在这里，我们表明，FGF诱导剂量依赖性的持续激活ERK 1/2，与高（纤维分化）剂量的FGF和玻璃体，刺激和维持延长（长达18小时）的ERK 1/2磷酸化配置文件。相比之下，较低（增殖）剂量的FGF，和水，刺激ERK 1/2磷酸化只有6小时。如果我们选择性地减少18小时ERK 1/2磷酸化的玻璃体诱导的6小时，通过特异性阻断FGF受体信号，玻璃体现在不能诱导透镜纤维分化，但保留的能力，诱导透镜细胞增殖。这些发现不仅提供了深入了解FGF在不同的眼部介质中发挥的重要作用，洗澡的透镜，但启发我们的一些假定的分子机制，其中一个特定的生长因子，在这种情况下，FGF，可以引起不同的细胞反应，在相同的细胞类型。
The ocular environment is important for the establishment and maintenance of lens growth patterns and polarity. In the anterior chamber of the eye, the aqueous humour regulates lens epithelial cell proliferation whereas in the posterior, the vitreous humour regulates the differentiation of the lens cells into fiber cells. Members of the fibroblast growth factor (FGF) growth factor family have been shown to induce lens epithelial cells to undergo cell division and differentiate into fibers, with a low dose of FGF able to induce cell proliferation (but not fiber differentiation), and higher doses required to induce fiber differentiation. Both these cellular events have been shown to be regulated by the MAPK/ERK1/2 signalling pathway. In the present study, to better understand the contribution of ERK1/2 signalling in regulating lens cell proliferation and differentiation, we characterized the ERK1/2 signalling profiles induced by different doses of FGF, and compared these to those induced by the different ocular media. Here, we show that FGF induced a dose-dependent sustained activation of ERK1/2, with both a high (fiber differentiating) dose of FGF and vitreous, stimulating and maintaining a prolonged (up to 18 hr) ERK1/2 phosphorylation profile. In contrast, a lower (proliferating) dose of FGF, and aqueous, stimulated ERK1/2 phosphorylation for only up to 6 hr. If we selectively reduce the 18 hr ERK1/2 phosphorylation profile induced by vitreous to 6 hr, by specifically blocking FGF receptor signalling, the vitreous now fails to induce lens fiber differentiation but retains the ability to induce lens cell proliferation. These findings not only provide insights into the important role that FGF plays in the different ocular media that bathe the lens, but enlighten us on some of the putative molecular mechanisms by which one specific growth factor, in this case FGF, can elicit a different cellular response in the same cell type.