Growth-factor induced signalling pathways involved in the regulation of lens cell behaviour

生长因子诱导的信号通路参与晶状体细胞行为的调节

• 批准号: nhmrc : 301939
• 负责人: Prof Frank Lovicu
• 金额: $ 16.9万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/growth-factor-induced-cell-behaviour/81258
• 关键词: Growth; factor; induced; signalling; pathways

Cataract, the loss of transparency of the eye lens, is a major cause of blindness in the world. 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 precise localised differentiation into fibres. As disruption of this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation may provide insights into the mechanisms involved in cataract formation. Following cataract surgery, for example, a number of patients develop aftercataract which results from the response of lens cells remaining after surgery. These residual cells, unlike those tightly regulated in the normal lens, begin to divide and differentiate in an attempt to form a new lens. The main aim of this study is to understand what regulates the proliferation and differentiation of lens cells. Growth factors are key regulators of cell behaviour and our studies provide evidence that members of the FGF, PDGF and IGF growth factor families play pivotal roles in the lens by influencing cell proliferation and differentiation. Growth factors stimulate cellular processes by activating specific cell surface receptors. Once activated, these receptors switch on specific intracellular signalling pathways leading to a specific cellular response. To understand how different growth factors mediate and regulate lens cell proliferation and fibre differentiation, we plan to examine the role of FGF-, PDGF- and IGF-induced signalling in normal lens biology. To do this, we will use a well established lens explant culture system to dissect the signalling pathway(s) downstream of specific receptor activation and correlate this with a specific cellular response. By understanding the 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，是世界上失明的主要原因。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它们向纤维的精确定位分化来调节。由于这一严密调控的破坏会导致白内障，识别控制细胞增殖和分化的分子可能有助于深入了解白内障形成的机制。例如，在白内障手术后，许多患者会出现后发性白内障，这是由于手术后残留的晶状体细胞的反应造成的。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，它们开始分裂和分化，试图形成新的晶状体。这项研究的主要目的是了解是什么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，表明成纤维细胞生长因子、PDGF和IGF生长因子家族的成员通过影响细胞的增殖和分化在晶状体中发挥关键作用。生长因子通过激活特定的细胞表面受体来刺激细胞过程。一旦被激活，这些受体就会启动特定的细胞内信号通路，导致特定的细胞反应。为了了解不同的生长因子如何调节晶状体细胞的增殖和纤维分化，我们计划研究成纤维细胞生长因子、血小板衍生生长因子和胰岛素样生长因子诱导的信号在正常晶状体生物学中的作用。为此，我们将使用成熟的晶状体外植体培养系统来剖析特定受体激活下游的信号通路(S)，并将其与特定的细胞反应相关联。通过了解晶状体正常发育所必需的细胞过程，我们可以更好地理解这些过程的中断是如何导致白内障的形成。