The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis.
The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis.
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成纤维细胞生长因子受体底物 2 (FRS2) 在调节小鼠附睾细胞外信号调节激酶 (ERK) 通路成分的两个活性水平中的作用。
DOI：
10.1095/biolreprod.112.107185
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发表时间：
2013
影响因子：
3.6
通讯作者：
Hinton,BarryT
中科院分区：
文献类型：
--
作者：
Xu,Bingfang;Yang,Ling;Hinton,BarryT
细胞外信号调节激酶（ERK）通路的组分参与附睾细胞过程的调节。有趣的是，我们以前的研究表明，有两个不同的活性水平的ERK途径的成分在附睾上皮：在大多数地区的基础水平和较高的水平，在分化的初始段（IS）。在这项研究中，我们分析了成纤维细胞生长因子受体底物2（FRS2）在这两个水平的调节作用。产生两种小鼠模型。在第一个模型中，从胚胎期开始，除IS外，大多数附睾区域的上皮细胞中Frs2被删除。Frs 2的缺失抑制了ERK通路组分的基础活性水平，这导致了附睾管沿着凋亡的增加。这在野生型附睾中FRS2表达水平最高的时期观察到。在第二个模型中，从出生后第17天开始，从近端附睾上皮中删除Frs2。该模型中的大多数附睾表现出正常形态。这些附睾中Frs2的缺失并不影响IS中ERK通路组分的高活性水平。然而，第二个模型中的附睾亚组显示细胞凋亡增加，导致近端区域形状异常或肉芽肿的发展。因此，这两种模型的数据表明，FRS2在调节附睾中ERK通路组分的两种活性水平中发挥不同的作用。
The components of the extracellular signal-regulated kinase (ERK) pathway are involved in the regulation of epididymal cellular processes. Interestingly, our previous studies showed that there are two different activity levels of the ERK pathway components in the epididymal epithelium: a basal level in most regions and a higher level in the differentiated initial segment (IS). In this study we analyzed the role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of these two levels. Two mouse models were generated. In the first model,Frs2was deleted from epithelial cells of most epididymal regions except for the IS from the embryonic period onward. Loss ofFrs2dampened the basal activity level of the ERK pathway components, which resulted in an increase in apoptosis along the epididymal duct. This was observed during the period when FRS2 expression level was highest in wild-type epididymides. In the second model,Frs2was deleted from the proximal epididymal epithelium from Postnatal Day 17 onward. Most of the epididymides in this model exhibited normal morphology. Loss ofFrs2in these epididymides did not affect the high activity level of the ERK pathway components in the IS. However, a subgroup of epididymides in the second model showed increased apoptosis which resulted in an abnormally shaped proximal region or development of granulomas. Therefore, data from these two models showed that FRS2 played different roles in the regulation of two activity levels of the ERK pathway components in the epididymis.