Vascular Endothelial Growth Factor A and Leptin Expression Associated with Ectopic Proliferation and Retinal Dysplasia in Zebrafish Optic Pathway Tumors.
Vascular Endothelial Growth Factor A and Leptin Expression Associated with Ectopic Proliferation and Retinal Dysplasia in Zebrafish Optic Pathway Tumors.
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DOI：
10.1089/zeb.2016.1366
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发表时间：
2017-08
期刊：
影响因子：
2
通讯作者：
McGrail M
中科院分区：
文献类型：
--
作者：
Schultz LE;Solin SL;Wierson WA;Lovan JM;Syrkin-Nikolau J;Lincow DE;Severin AJ;Sakaguchi DS;McGrail M
在中枢神经系统中，损伤诱导细胞重编程和祖细胞增殖，但限制再生和防止肿瘤发生的分子机制尚不完全清楚。我们之前描述了一种斑马鱼视路肿瘤模型，在该模型中，转基因TG(flk1：RFP)为18/+的成年人发展为非恶性视网膜肿瘤。驱动损伤诱导的胶质细胞重编程和再生的关键通路有助于肿瘤的形成。在这项研究中，我们检查了增殖的时间过程，并提出了新的TG(flk1：RFP)是18/+发育不良的视网膜和肿瘤转录本的分析。视网膜发育不良首先在3个月大的成人中发现，但并不局限于特定的干细胞或祖细胞利基。通路分析表明，细胞呼吸减少、HIF1-α、血管内皮细胞生长因子、mTOR、核因子κβ和多种白介素化途径的表达增加与早期视网膜发育不良有关。HIF-α靶标VEGFA(VEGFAB)和瘦素(LEPB)在发育不良的视网膜中均高度上调；然而，它们分别在神经元和胶质细胞中表现出不同的表达模式。磷酸化S6免疫标记表明，在野生型视网膜、发育不良的视网膜和晚期肿瘤中，mTOR信号在多种细胞群中被激活。我们的结果提示，在这个视路肿瘤模型中，多条途径可能有助于视网膜前体细胞的持续增殖和肿瘤的生长。对这些信号通路的进一步研究可能会深入了解神经系统再生过程中控制增殖反应的潜在机制。
In the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes. Retinal dysplasia was first detected in 3-month-old adults, but was not limited to a specific stem cell or progenitor niche. Pathway analyses suggested a decrease in cellular respiration and increased expression of components of Hif1-α, VEGF, mTOR, NFκβ, and multiple interleukin pathways are associated with early retinal dysplasia. Hif-α targets VEGFA (vegfab) and Leptin (lepb) were both highly upregulated in dysplastic retina; however, each showed distinct expression patterns in neurons and glia, respectively. Phospho-S6 immunolabeling indicated that mTOR signaling is activated in multiple cell populations in wild-type retina and in the dysplastic retina and advanced tumor. Our results suggest that multiple pathways may contribute to the continuous proliferation of retinal progenitors and tumor growth in this optic pathway tumor model. Further investigation of these signaling pathways may yield insight into potential mechanisms to control the proliferative response during regeneration in the nervous system.
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影响因子：
14.9
作者：
Benita Y;Kikuchi H;Smith AD;Zhang MQ;Chung DC;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
20.1
作者：
Bouloumié, A;Drexler, HCA;Busse, R
通讯作者：
Busse, R
影响因子：
5.3
作者：
Diekmann, Heike;Kalbhen, Pascal;Fischer, Dietmar
通讯作者：
Fischer, Dietmar
影响因子：
4.6
作者：
Baird AM;Gray SG;Richard DJ;O'Byrne KJ
通讯作者：
O'Byrne KJ
影响因子：
4.6
作者：
Hashimoto, Takao;Zhang, Xiang-Mei;Yang, Xian-Jie
通讯作者：
Yang, Xian-Jie