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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760586
• 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。细胞外基质曾经只被视为将细胞组织成组织的惰性支架，现在已经变得重要，它通过整合素黏附分子提供必要的信号，这是控制细胞行为所必需的，包括细胞的增殖、分化和存活。然而，调控ECM信号转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，已知调节调节ECM-细胞结合和信号传递的事件。因此，基质细胞蛋白为理解基质和细胞通讯之间的细节提供了一种新的途径。为了最好地概括细胞外基质-细胞通讯所涉及的机制，我们将使用成纤维细胞作为细胞模型，因为这些细胞对细胞外基质信号具有丰富的反应机制，从而产生大量不同的基质蛋白。这种成纤维细胞的反应被称为成纤维细胞到肌成纤维细胞的转变(FMT)，发生在需要细胞外基质重塑的生物学过程中，即发育。我们最近发现了几个在细胞外基质重塑的成纤维细胞模型中上调的基质细胞蛋白基因。在这些基因中，MGP是首选候选基因之一，目前正被用来了解基质细胞蛋白如何通过FMT过程激活细胞通路，同时也成功地验证了我们长期计划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细胞外基质中“未被研究”的作用的基本概念，其信号可能像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培训机会，这将使加拿大人和整个科学界受益。尽管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仿生材料所需的基质工程技术进步提供基础，这些材料是ECM的类似物。总体而言，我们的MGP研究将成为从我们的RNA数据中发现其他母细胞蛋白质的平台，以建立我们未来的母细胞蛋白质研究计划。