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。胶原蛋白创造了一个细胞生存的环境，并形成纤维，使组织能够适应外部压力，例如在正常运动过程中发生的机械负荷。胶原蛋白可以被细胞利用生物酶分解和改造；生长发育中的正常过程。然而，癌细胞通过降解胶原蛋白侵入组织，同时制造自己不可降解的胶原蛋白，从而为入侵创造了途径。不可降解的胶原蛋白也被发现存在于退行性骨骼疾病，如骨关节炎和骨质疏松症，以及纤维化疾病，包括肝硬化。其他仅有的关于不可降解胶原蛋白的报道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，并实现正常的生物功能。干细胞有可能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。胚胎干细胞可以在体内形成所有类型的细胞，但由于伦理方面的考虑，它们在研究和治疗试验中的应用受到限制。成体组织干细胞是罕见的，可能只能再生它们来自的组织，但它们有可能用于治疗患者，而不会产生免疫排斥反应。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胶原蛋白产生的基因。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。这项研究对干细胞的特征和了解它们在富含胶原的组织的修复和再生中的作用是重要的。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，将有助于开发与年龄和疾病相关的胶原蛋白的生物标志物。这样的生物标记可以被纳入检测，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行动不便的速度，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项目提供信息。

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.