Collagen (I) homotrimer in age-related fibroses and tissue degeneration: evaluation as a stem cell biomarker

胶原蛋白是人体内最丰富的结构蛋白。胶原蛋白创造了细胞驻留的环境，并形成使组织对外部应力有弹性的纤维，例如在机械负荷期间，如在正常运动期间发生的。胶原蛋白可以被细胞利用生物酶分解和重组;这是生长和发育过程中的正常过程。然而，癌细胞通过降解胶原蛋白侵入组织，同时制造它们自己的不可降解形式的胶原蛋白，从而创建侵入途径。在退行性骨骼疾病如骨关节炎和骨质疏松症以及纤维化疾病包括肝硬化中也发现了不可降解的胶原。其他关于不可降解胶原蛋白的报道仅来自胚胎细胞或组织，这表明它可能是由一种干细胞产生的，并具有正常的生物学功能。干细胞有潜力形成许多不同的组织类型，它们的使用有可能彻底改变再生医学和组织工程的方法。胚胎干细胞可以形成体内的所有细胞类型，但由于伦理考虑，它们在研究和治疗试验中的使用受到限制。成人组织干细胞是罕见的，可能只能再生它们来自的组织，但它们可能被用于治疗它们被分离出来的患者，而不会产生随后的免疫排斥反应。该项目的目的是确定胚胎和/或成体干细胞是否产生不可降解的胶原蛋白，并了解细胞如何控制负责这种类型胶原蛋白生产的基因。该项目将研究衰老如何影响这两种形式的胶原蛋白的表达，并可能导致疾病。这项研究对于研究干细胞以及了解它们在富含胶原蛋白的组织的修复和再生中的作用非常重要。更清楚地了解特定类型的胶原蛋白在衰老和疾病中的作用将允许开发与年龄和疾病相关的胶原蛋白的生物标记物。这种生物标记可以被纳入测试，以确定一个人患癌症，关节炎或骨质疏松症等疾病的可能性。它们还可以用来预测一个人在老年时变得虚弱和不动的速度，从而为特定群体量身定制生活方式建议（饮食，运动，建筑环境）和未来的抗衰老药物。该项目的结果将为旨在将干细胞用于移植或组织工程的研究计划提供信息。

Collagen is the most abundant structural protein in the body. Collagen creates an environment within which cells reside and forms fibres that make tissues resilient to external stresses, for example during mechanical loading such as that occurs during normal locomotion. Collagen can be broken down and reformed by cells using biological enzymes; a normal process during growth and development. However, cancer cells invade tissues by degrading collagen whilst concurrently making their own non-degradable version of collagen, thereby creating a pathway for invasion. Non-degradable collagen has also been found in degenerative skeletal diseases such as osteoarthritis and osteoporosis as well as in fibrotic diseases including liver cirrhosis. The only other reports of non-degradable collagen are from embryonic cells or tissues, indicating that it might be produced by a type of stem cell and fulfil a normal biological function. Stem cells have the potential to form many different tissue types and their use has the potential to revolutionise approaches to regenerative medicine and tissue engineering. Embryonic stem cells can form all cell types in the body, but their use in research and in treatment trials is limited because of ethical considerations. Adult tissue stem cells are rare and may only be able to regenerate the tissue that they came from, but they could potentially be used to treat the patient from which they were isolated without subsequent immune rejection. The aim of this project is to determine whether non-degradable collagen is produced by embryonic and/or adult stem cells and to understand how cells control the genes responsible for this type of collagen production. This project will investigate how ageing affects the expression of these two forms of collagen and might predispose to disease. This research is important to characterise stem cells and to understand their role in the repair and regeneration of collagen-rich tissues. A clearer understanding of the role of particular types of collagen in ageing and disease would allow the development of biological markers for age- and disease-associated collagen. Such biological markers could be incorporated into tests to determine an individual's likelihood of developing diseases such as cancer, arthritis or osteoporosis. They could also be used to predict how quickly an individual might become frail and immobile in old age and to therefore tailor lifestyle recommendations (diet, exercise, built environment) and future anti-ageing medicines for particular groups. The results from this project would be informative for research programs that aim to use stem cells for transplantation or in tissue engineering.