Investigating the Dynamic Interplay between the Extracellular Matrix and Cellular Behaviour

研究细胞外基质与细胞行为之间的动态相互作用

• 批准号: RGPIN-2019-06366
• 负责人: Gerarduzzi, Casimiro
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738867
• 关键词: Investigating; Dynamic; Interplay; between; Extracellular

The Extracellular Matrix (ECM) is the structural microenvironment necessary for the physical support of the population of cells embedded within it. Once viewed as only an inert scaffold for organizing cells into tissues, the ECM has gained importance in providing essential signals through integrin adhesion molecules necessary for controlling cellular behaviour, including cell proliferation, differentiation and survival. However, the detailed molecular mechanisms governing ECM signalling have yet to be fully understood. Matricellular proteins are a recently classified group of active matrix proteins known to regulate events that modulate ECM-cellular binding and signalling. Therefore, matricellular proteins offer a novel approach to understand the details between the matrix and cellular communication. To best recapitulate the mechanisms implicated within ECM-cellular communication, we will use fibroblasts as a cellular model since these cells have a rich response mechanism to ECM signals to produce large amounts of various matrix proteins. This fibroblast response is known as Fibroblast-To-Myofibroblast Transition (FMT) and occurs during biological processes requiring ECM remodeling, i.e. development. We recently discovered several matricellular protein genes that were upregulated in a fibroblast model of ECM remodeling. Among those genes, MGP was one of the top selected candidates and is currently being used to understand how matricellular proteins activate cellular pathways through the FMT process, but also successfully validate the approach of studying matricellular proteins for our long-term program. Our research program will contribute to the understanding of the fundamental concepts underlying the `understudied' role of matricellular proteins in the ECM, whose signals could be as dynamic as an intracellular signalling cascade. The program also provides optimal training opportunities for innovative thinking, technological advancement and scientific discovery that will benefit Canadians and the whole scientific community. Although such discoveries would be pertinent to scientists studying molecular and cellular processes, they will also provide a basis for technological advancement in matrix engineering needed for the development of 2D-3D biomimetic materials that are ECM analogs. Overall, our MGP study will be the platform to other discovered matricellular proteins from our RNA data to build our future program in matricellular protein research.

细胞外基质（ECM）是为嵌入其中的细胞群体提供物理支持所必需的结构微环境。ECM曾经被认为只是将细胞组织成组织的惰性支架，但它在通过整合素粘附分子提供必要的信号以控制细胞行为（包括细胞增殖、分化和存活）方面发挥了重要作用。然而，控制ECM信号传导的详细分子机制尚未完全了解。基质细胞蛋白是最近分类的一组活性基质蛋白，已知可调节调节ecm细胞结合和信号传导的事件。因此，基质细胞蛋白提供了一种新的方法来了解基质和细胞通讯之间的细节。为了最好地概括与ECM-细胞通讯有关的机制，我们将使用成纤维细胞作为细胞模型，因为这些细胞对ECM信号具有丰富的反应机制，可以产生大量各种基质蛋白。这种成纤维细胞反应被称为成纤维细胞到肌成纤维细胞转化（FMT），发生在需要ECM重塑的生物过程中，即发育过程。我们最近发现几个基质细胞蛋白基因在ECM重塑的成纤维细胞模型中上调。在这些基因中，MGP是最受欢迎的候选基因之一，目前被用于了解基质细胞蛋白如何通过FMT过程激活细胞通路，同时也成功验证了我们长期项目研究基质细胞蛋白的方法。我们的研究计划将有助于理解基质细胞蛋白在ECM中“未被充分研究”的作用的基本概念，其信号可能与细胞内信号级联一样动态。该计划还为创新思维、技术进步和科学发现提供了最佳的培训机会，这将使加拿大和整个科学界受益。虽然这些发现与研究分子和细胞过程的科学家有关，但它们也将为开发2D-3D仿生材料（ECM类似物）所需的基质工程技术进步提供基础。总的来说，我们的MGP研究将成为从我们的RNA数据中发现其他基质细胞蛋白的平台，以建立我们未来的基质细胞蛋白研究计划。