TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells
TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells
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DOI：
10.1016/j.bbrc.2011.10.074
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发表时间：
2011-11-18
影响因子：
3.1
通讯作者：
Lee, Joon H.
中科院分区：
文献类型：
--
作者：
Chung, Eun Jee;Chun, Ji Na;Lee, Joon H.
III类β-微管蛋白亚型(β(III))仅由正常人视网膜内的神经元表达，而在正常视网膜色素上皮(RPE)细胞或原代培养的早期阶段不存在。然而，在特发性黄斑皱褶、增殖性玻璃体视网膜病变(PVR)和增殖性糖尿病视网膜病变(PDR)的病理性视网膜前膜中，已观察到III型β-微管蛋白在传代的RPE细胞和去分化的RPE细胞中异常表达。转化生长因子-β(TGF-β)与RPE细胞的去分化有关，在增殖性玻璃体视网膜疾病的发生发展中起重要作用。在这里，我们研究了转化生长因子-β对III型β-微管蛋白异常表达的潜在影响，以及介导这些变化的细胞内信号通路。用Western blotting、RT-PCR和免疫细胞化学方法检测转化生长因子-β诱导的RPE细胞中III型β-微管蛋白的异常表达和O-连接的β-N-乙酰氨基葡萄糖(O-GIcNAc)修饰。转化生长因子-β也能刺激ERK的磷酸化。ERK磷酸化抑制剂U0126可显著降低转化生长因子-β诱导的III型β-微管蛋白的异常表达。我们的发现表明，转化生长因子-β通过激活ERK信号通路刺激III类β-微管蛋白的异常表达。这些数据表明，成熟的RPE细胞具有在转化生长因子-β刺激下表达神经元相关基因的能力，并为了解增生性玻璃体视网膜疾病的发病机制提供了有用的信息。(C)2011 Elsevier Inc.保留所有权利。
The class III beta-tubulin isotype (beta(III)) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III beta-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-beta(TGF-beta) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-beta on the aberrant expression of class III beta-tubulin and the intracellular signaling pathway mediating these changes. TGF-beta-induced aberrant expression and O-linked-beta-N-acetylglucosamine (O-GIcNac) modification of class III beta-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-beta also stimulated phosphorylation of ERK. TGF-beta-induced aberrant expression of class III beta-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-beta stimulated aberrant expression of class III beta-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-beta stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases. (C) 2011 Elsevier Inc. All rights reserved.