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.

白内障是眼镜镜的透明度的丧失，是世界上失明的主要原因。白内障的治疗取决于对正常和白内障晶状体中分子过程的更好理解。晶状体生长受到上皮细胞的受控增殖及其精确的局部分化为纤维的调节。由于这种严格的调节会导致白内障，因此确定控制细胞增殖和分化的分子可能会提供有关白内障形成所涉及的机制的见解。例如，在白内障手术后，许多患者会出现腹腔治疗，这是由于手术后剩余的晶状体细胞反应而导致的。这些残留细胞与在正常镜头中受到严格调节的细胞开始分裂和区分，以尝试形成新的晶状体。这项研究的主要目的是了解是什么调节了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，FGF，PDGF和IGF生长因子家族的成员通过影响细胞增殖和分化而在镜头中起关键作用。生长因子通过激活特定的细胞表面受体刺激细胞过程。一旦激活，这些受体会打开特定的细胞内信号传导途径，从而导致特定的细胞反应。为了了解不同的生长因子如何介导和调节晶状体细胞增殖和纤维分化，我们计划检查FGF-，PDGF-和IGF诱导的信号在正常晶状体生物学中的作用。为此，我们将使用良好的透镜外植体培养系统来剖析特定受体激活的下游信号传导途径，并将其与特定的细胞反应相关联。通过了解正常晶状体发育必不可少的细胞过程，我们可以更好地了解这些过程的破坏是如何导致白内障形成的。