Regulation of lens cell behaviour by RTK antagonists, Sef and Sprouty.

RTK 拮抗剂 Sef 和 Sprouty 对晶状体细胞行为的调节。

• 批准号: nhmrc : 457336
• 负责人: Prof Frank Lovicu
• 金额: $ 21.3万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-lens-cell-sef-sprouty/97458
• 关键词: Regulation; lens; cell; behaviour; RTK

Cataract, the loss of transparency of the eye lens, is a major cause of world blindness. A cure for cataract depends on a better understanding of the molecular processes in the normal and cataractous lens. Lens growth is regulated by controlled proliferation of epithelial cells and their localised differentiation into fibres. As disruption to this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation will provide insights into the mechanisms involved in cataract formation. Following cataract surgery, for example, many patients develop aftercataract which results from residual lens cells. These residual cells, unlike those tightly regulated in the normal lens, divide and differentiate to form a secondary cataract. The main aim of this study is to understand what molecules regulate the proliferation and differentiation of lens cells. Growth factors are key regulators of cell behaviour and our studies provide evidence that FGF growth factors play pivotal roles in the lens by influencing cell proliferation and differentiation. We have recently identified inhibitors of FGF in the lens, called Sprouty and Sef; molecules shown in other systems to effectively block FGF intracellular signalling pathways. To understand how Sef and Sprouty regulate lens cell proliferation and fibre differentiation, we plan to examine what regulates their expression, and more importantly their role in FGF-induced cell signalling in normal lens biology. To do this, we will use a well established explant culture system to monitor the effectiveness of these endogenous inhibitors on growth factor-induced lens cell proliferation and differentiation, as well as use transgenic mice technology to determine the role they play in situ. By understanding the molecular and cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.

白内障，即眼睛晶状体透明度的丧失，是导致世界失明的主要原因。白内障的治愈取决于对正常晶状体和白内障晶状体分子过程的更好理解。晶状体的生长由上皮细胞的受控增殖和局部分化成纤维来调节。由于这一严格调控的中断会导致白内障，识别控制细胞增殖和分化的分子将为深入了解白内障形成的机制提供帮助。例如，在白内障手术后，许多患者会出现后发性白内障，这是由于晶状体细胞残留造成的。这些残留细胞与正常晶状体中那些受到严格调控的细胞不同，它们分裂分化形成继发性白内障。这项研究的主要目的是了解哪些分子调节晶状体细胞的增殖和分化。生长因子是细胞行为的关键调节因子，我们的研究提供了证据，证明成纤维细胞生长因子通过影响细胞的增殖和分化在晶状体中发挥关键作用。我们最近在晶状体中发现了成纤维细胞生长因子的抑制剂，称为Sprouty和Sef；在其他系统中显示的分子可以有效地阻断成纤维细胞生长因子的细胞内信号通路。为了了解SEF和Sprouty如何调控晶状体细胞的增殖和纤维分化，我们计划研究是什么调节了它们的表达，更重要的是，它们在正常晶状体生物学中由成纤维细胞生长因子诱导的细胞信号转导中所扮演的角色。为此，我们将使用成熟的外植体培养系统来监测这些内源性抑制物对生长因子诱导的晶状体细胞增殖和分化的有效性，并使用转基因小鼠技术来确定它们在原位所起的作用。通过了解正常晶状体发育所必需的分子和细胞过程，我们可以更好地了解这些过程的中断是如何导致白内障的形成。