Molecular analysis of hyaluronan

这项工作旨在了解一种名为“透明质酸”的长吸水分子的功能，这种分子在哺乳动物的发育中起着至关重要的作用，它被认为为祖细胞的增殖提供了一个支持性的生态位。它在组织损伤后迅速诱导，以协助修复过程，但它是如何帮助的尚不清楚。我们的整体研究计划旨在了解透明质酸在体内的功能，以及它如何与细胞表面受体CD44相互作用。在这个提议中，我们将评估透明质酸在伤口修复过程的三个阶段的贡献：1)炎症期，2)增殖期和3)溶解期。我们将确定诱导透明质酸表达和调节其转换的因素，确定透明质酸在组织中免疫细胞募集中的作用，并确定它在反应的增殖阶段有多重要。这将提供基本的新知识，有助于我们理解组织更新和修复，以及免疫系统如何帮助这一过程。这一新知识将有助于查明透明质酸在组织重塑中的作用，并将帮助科学家更好地了解伤口修复过程。透明质酸在组织更新和修复中的作用也适用于其他透明质酸普遍存在的生物学领域，如发育和干细胞更新。这项工作还可能为帮助开发促进组织修复和预防瘢痕形成的新策略提供所需的基础知识。此外，更好地了解透明质酸在免疫募集和细胞更新中的作用，在开发旨在支持组织再生的人工基质方面具有广阔的应用前景。这项研究将对免疫学家、生物学家和生物工程师有用，他们可以利用新的信息来设计新的应用和开发促进组织再生和推进损伤治疗的新技术。这项研究还将涉及培养具有创新思维、创造性科学发现和使用尖端技术的高素质人才。新知识、训练有素的人员和潜在的新技术应用都将有利于加拿大和更广泛的国际科学界。

This works seeks to understand the function of a long water-absorbing molecule called “hyaluronan” that plays an essential role in mammalian development where it is thought to provide a supportive niche for progenitor cells to proliferate. It is rapidly induced in tissues upon damage to assist in the repair process but how it helps is not understood. Our overall research program is aimed at understanding the function of hyaluronan in the body and how it interacts with its cell surface receptor, CD44. In this proposal we will evaluate the contribution of hyaluronan in the three phases of the wound repair process: 1) the inflammatory phase, 2) the proliferative phase and 3) the resolution phase. We will determine the factors that induce hyaluronan expression and regulate its turnover, determine the role hyaluronan plays in immune cell recruitment in the tissue and determine how important it is for the proliferation phase of the response. This will provide fundamental new knowledge that will help in our understanding of tissue renewal and repair and how the immune system helps this process. This new knowledge will help pinpoint hyaluronan's action in tissue remodeling and will help scientists better understand the wound repair process. The role of hyaluronan in tissue renewal and repair will also be applicable to other areas of biology where hyaluronan is prevalent such as in development and in stem cell renewal. This work may also provide the basic knowledge required to help develop new strategies to promote tissue repair and prevent scarring. Furthermore, a better understanding of how hyaluronan functions in immune recruitment and in cell renewal has promising applications in the development of artificial matrices designed to support tissue regeneration. This research will be of use to immunologists, biologists and bio-engineers who can use the new information to design new applications and develop new technologies that promote tissue regeneration and advance the treatment of injuries. This research will also involve the training highly qualified personnel in innovative thinking, inventive scientific discovery and the use of cutting edge technologies. The new knowledge, the high trained personnel and the potential new technological applications will all be of benefit to Canada and the broader international scientific community.