Expression of cytokine signal transduction components in the postnatal mouse retina.
Expression of cytokine signal transduction components in the postnatal mouse retina.
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发表时间：
2003-12
期刊：
影响因子：
2.2
通讯作者：
K. Rhee;Xian-Jie Yang
中科院分区：
文献类型：
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作者：
K. Rhee;Xian-Jie Yang
睫状神经营养因子（CNTF）家族的细胞因子在视网膜发育过程中影响神经元的分化，并在各种视网膜变性模型中提高细胞存活率。然而，CNTF信号转导的细胞机制和CNTF在发育中的视网膜中的靶细胞类型仍然不清楚。本研究的目的是表征参与细胞因子信号转导的蛋白质在小鼠视网膜中的表达模式，从而评估不同视网膜细胞类型对CNTF样细胞因子信号的潜在反应性。方法采用免疫组织化学方法检测不同出生后阶段小鼠视网膜组织中CNTF受体α（CNTFRa）和gp 130、细胞内蛋白激酶Jak 2和Tyk 2以及潜在转录因子STAT 1和STAT 3的表达。免疫荧光染色观察ERK的分布。结果在新生小鼠视网膜中，gp 130、CNTFR α、Jak 2、Tyk 2、STAT 1和STAT 3在分化的神经节细胞层和发育中的内丛状层中存在强染色信号。在出生后早期小鼠视网膜的脑室区也观察到可检测的染色信号。从P5到P10，细胞因子信号分子也在发育中的外丛状层中积累。在成人视网膜中，细胞因子信号成分检查被定位到神经节细胞层，内核层，和两个丛状层。此外，对应于感光细胞的内节和/或外节的区域显示细胞因子信号传导组分的阳性染色。与此相反，ERK 2蛋白激酶被发现在整个新生儿视网膜。在成熟视网膜中，ERK 2集中在神经节细胞和内丛状层，而在内核层、外丛状层和外核层检测到较少的ERK 2表达。结论：在新生小鼠视网膜中，Jak-STAT信号通路和ERK 2的信号成分差异表达。本研究中包括的所有细胞因子信号传导组分在分化的内层视网膜以及占据脑室区的细胞中表达，这表明有丝分裂后神经元和增殖祖细胞在出生后发育期间可能直接响应CNTF样细胞因子。细胞因子信号通路组分在成年小鼠视网膜中的分布与先前的发现一致，即神经节细胞和Müller胶质细胞是CNTF的主要靶细胞类型。
PURPOSE Members of the ciliary neurotrophic factor (CNTF) family of cytokines have been shown to influence neuronal differentiation during retinal development and enhance cell survival in various retinal degeneration models. However, the cellular mechanism of CNTF signaling and the target cell types for CNTF in the developing retina remain unidentified. The purpose of this study is to characterize expression patterns of proteins involved in cytokine signal transduction in the mouse retina, thus to assess the potential responsiveness of different retinal cell types to CNTF-like cytokine signals. METHODS The expression profiles of various cytokine signal transduction components, including receptor subunits CNTF receptor alpha (CNTFRa) and gp130, intracellular protein kinases, Jak2 and Tyk2, as well as latent transcription factors, STAT1 and STAT3, were determined by immunohistochemical staining of mouse retinal sections derived from different postnatal stages. In addition, the distribution of ERK was studied by immunofluorescent staining. RESULTS In the neonatal retina, intense staining signals for gp130, CNTFRalpha, Jak2, Tyk2, STAT1, and STAT3 were present in the differentiated ganglion cell layer and the developing inner plexiform layer of the mouse retina. Detectable staining signals were also observed in the ventricular zone of the early postnatal mouse retina. From P5 to P10, cytokine signaling molecules also accumulated in the developing outer plexiform layer. In the adult retina, cytokine signaling components examined were localized to the ganglion cell layer, the inner nuclear layer, and the two plexiform layers. In addition, regions corresponding to the inner and/or outer segments of the photoreceptor cells showed positive staining for cytokine signaling components. In contrast, the ERK2 protein kinase was found throughout the neonatal retina. In the mature retina, ERK2 was concentrated in the ganglion cells and the inner plexiform layer, while a lesser expression of ERK2 was detected in the inner nuclear layer, the outer plexiform layers, and the outer nuclear layer. CONCLUSIONS In the neonatal mouse retina, signaling components of the Jak-STAT pathway and ERK2 are differentially expressed. All cytokine signaling components included in this study are expressed in the differentiated inner retina as well as in cells occupying the ventricular zone, suggesting that both postmitotic neurons and proliferative progenitors may directly respond to CNTF-like cytokines during postnatal development. The distribution of cytokine signaling pathway components in the adult mouse retina is consistent with previous findings that ganglion cells and Müller glia are the primary target cell types for CNTF.