The role of PCKalpha and modulation of desmosomal adhesion in delayed wound healing in the elderly

PCKα 和桥粒粘附调节在老年人伤口愈合延迟中的作用

• 批准号: G0800004/1
• 负责人: Matthew Hardman
• 金额: $ 52.18万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800004%2F1
• 关键词: role; PCKalpha; modulation; desmosomal; adhesion

Wounds to the skin do not always heal quickly and over time can lead to disability, distress, or even death, and huge health care costs. This problem is increasing as we have more people in the elderly at-risk age-group, but we do not yet fully understand why older people have poor healing. Skin wounds heal through a complex series of events, which are carefully regulated and involve several cell types. Our group have shown that the female hormone estrogen has a beneficial effect on healing, and acts upon all of the different cell types in a wound. Our understanding of the effects of age on the upper skin layer (the epidermis) and reformation of the outer skin barrier is particularly poor. Recent studies from our laboratory, comparing how wounds from old and young subjects heal, have identified cell adhesion in this upper skin layer (conferred by specialised structures called desmosomes) as a key process that leads to poor healing in the elderly. Furthermore, we have shown that desmosomes undergo specific changes after the skin is wounded. These new studies are essential to answer a number of important questions including how these changes are regulated and the implications for improving delayed healing in the elderly. Our work will initially use cultured cells and mice modified to express desmosomal proteins to understand the biology. This will direct experiments on human samples that will ultimately lead to the development of new treatments to accelerate healing in the elderly.

皮肤伤口并不总是很快愈合，随着时间的推移可能导致残疾，痛苦，甚至死亡，以及巨大的医疗保健费用。这个问题正在增加，因为我们有更多的人在老年人的风险年龄组，但我们还没有完全理解为什么老年人有穷人愈合。皮肤伤口通过一系列复杂的事件愈合，这些事件受到仔细调节并涉及几种细胞类型。我们的研究小组已经表明，女性激素雌激素对愈合有有益的影响，并作用于伤口中所有不同类型的细胞。我们对年龄对上皮肤层（表皮）的影响和外部皮肤屏障的重建的理解特别差。我们实验室最近的研究比较了老年人和年轻人的伤口愈合情况，已经确定了皮肤上层的细胞粘附（由称为桥粒的特殊结构赋予）是导致老年人愈合不良的关键过程。此外，我们已经表明，皮肤受伤后，桥粒经历特定的变化。这些新的研究对于回答一些重要的问题至关重要，包括这些变化是如何调节的，以及对改善老年人延迟愈合的影响。我们的工作将首先使用培养的细胞和小鼠修饰表达桥粒蛋白，以了解生物学。这将指导对人体样本的实验，最终导致开发新的治疗方法，以加速老年人的愈合。