Epithelial phenotype and the RPE: is the answer blowing in the Wnt?
Epithelial phenotype and the RPE: is the answer blowing in the Wnt?
复制标题
上皮表型和RPE：答案是否在Wnt中吹来？
DOI：
10.1016/j.preteyeres.2008.08.002
复制
发表时间：
2008-11
影响因子：
17.8
通讯作者：
Burke, Janice M.
中科院分区：
文献类型：
--
作者：
Burke, Janice M.
人视网膜色素上皮 (RPE) 细胞在原位组织内具有规则的上皮细胞形状，但由于仍难以捉摸的原因，RPE 在体外增殖后表现出不完整且可变的重新形成上皮表型的能力。在其他上皮细胞培养物中，由 E-钙粘蛋白组成的粘附连接 (AJ) 的形成在上皮形态发生中发挥重要的早期诱导作用，但 RPE 中基本上不存在 E-钙粘蛋白。在本综述中，讨论了次要钙粘蛋白（E-钙粘蛋白）和主要钙粘蛋白（N-钙粘蛋白）对 RPE 表型发育的贡献。重点放在 AJ 组装过程中肌动蛋白细胞骨架重塑的未来研究的重要性，AJ 组装过程中，上皮细胞中的肌动蛋白组织会形成典型的小带状肌动蛋白组织。描述了用于测量 RPE 培养物成熟状态的 RPE 表型的其他标记，包括组织特异性蛋白质表达、蛋白质极性和色素沉着。有人认为，RPE 上皮表型、基于钙粘蛋白的细胞间粘附和黑化通过共同的信号传导途径：Wnt/β-连环蛋白途径相关。建议分析该通路及其交叉信号网络作为剖析 RPE 形态发生步骤的有用框架。还讨论了衰老对 RPE 表型的影响。初步证据表明，光诱导的 ARPE-19 细胞亚致死氧化应激会损害细胞器运动。由应激敏感的细胞骨架支架介导的细胞器易位是细胞表型发育和保留的重要过程。因此，对细胞器运动受损的观察提出了一种可能性，即低水平的压力（据信伴随 RPE 老化）可能会对细胞表型产生微妙的破坏。随着时间的推移，这些预计会削弱 RPE 代表光感受器执行的支持功能，理论上会导致老年性视网膜疾病，例如年龄相关性黄斑变性 (AMD)。分析导致 RPE 功能效率下降而不是明显细胞死亡的亚致死压力被认为是了解年龄对 RPE 组织和生理学影响的有用的未来方向。至于表型和色素沉着，Wnt/β-连环蛋白途径也被认为在调节 RPE 对氧化应激的反应中发挥着作用。因此，探索 RPE 中的这条通路可能会提供一个统一的策略，以促进我们对 RPE 表型以及轻度氧化应激对 RPE 结构和功能的影响的理解。
Cells of the human retinal pigment epithelium (RPE) have a regular epithelial cell shape within the tissue in situ, but for reasons that remain elusive the RPE shows an incomplete and variable ability to re-develop an epithelial phenotype after propagation in vitro. In other epithelial cell cultures, formation of an adherens junction (AJ) composed of E-cadherin plays an important early inductive role in epithelial morphogenesis, but E-cadherin is largely absent from the RPE. In this review, the contribution of cadherins, both minor (E-cadherin) and major (N-cadherin), to RPE phenotype development is discussed. Emphasis is placed on the importance for future studies of actin cytoskeletal remodeling during assembly of the AJ, which in epithelial cells results in an actin organization that is characteristically zonular. Other markers of RPE phenotype that are used to gauge the maturation state of RPE cultures including tissue-specific protein expression, protein polarity, and pigmentation are described. An argument is made that RPE epithelial phenotype, cadherin-based cell–cell adhesion and melanization are linked by a common signaling pathway: the Wnt/β-catenin pathway. Analyzing this pathway and its intersecting signaling networks is suggested as a useful framework for dissecting the steps in RPE morphogenesis. Also discussed is the effect of aging on RPE phenotype. Preliminary evidence is provided to suggest that light-induced sub-lethal oxidative stress to cultured ARPE-19 cells impairs organelle motility. Organelle translocation, which is mediated by stress-susceptible cytoskeletal scaffolds, is an essential process in cell phenotype development and retention. The observation of impaired organelle motility therefore raises the possibility that low levels of stress, which are believed to accompany RPE aging, may produce subtle disruptions of cell phenotype. Over time these would be expected to diminish the support functions performed by the RPE on behalf of photoreceptors, theoretically contributing to aging retinal disease such as age-related macular degeneration (AMD). Analyzing sub-lethal stress that produces declines in RPE functional efficiency rather than overt cell death is suggested as a useful future direction for understanding the effects of age on RPE organization and physiology. As for phenotype and pigmentation, a role for the Wnt/β-catenin pathway is also suggested in regulating the RPE response to oxidative stress. Exploration of this pathway in the RPE therefore may provide a unifying strategy for advancing our understanding of both RPE phenotype and the consequences of mild oxidative stress on RPE structure and function.
登录
查看更多内容
影响因子：
11.2
作者：
Alonso, Soledad R.;Tracey, Lorraine;Rodriguez-Peralto, Jose L.
通讯作者：
Rodriguez-Peralto, Jose L.
影响因子：
4.4
作者：
Burke, Janice M.;Hong, Jeehee
通讯作者：
Hong, Jeehee
影响因子：
5.5
作者：
Banan, A;Zhang, LJ;Keshavarzian, A
通讯作者：
Keshavarzian, A
影响因子：
14.8
作者：
Agrawal, Rajat N.;He, Shikun;Hinton, David R.
通讯作者：
Hinton, David R.
影响因子：
4.8
作者：
Aslan, M;Ryan, TM;Freeman, BA
通讯作者：
Freeman, BA