GlyCORE: Glycoscience Center of Research Excellence

项目摘要 了解损伤后的组织愈合和蛋白质表达在再生医学中至关重要。的 糖蛋白CTHRC 1在组织修复、脂肪细胞形成的调节和骨发育中起重要作用。 它由活化的成纤维细胞产生，有助于代谢效率和内皮细胞的存活， 其在愈合期间维持体内平衡和毛细血管网络。然而，CTHRC 1的异常表达是 在慢性炎症以及恶性生长中观察到。虽然糖基化对于适当的 尽管糖基化是许多分泌蛋白质的重要功能，但我们还不了解糖基化如何影响其有益作用 CTHRC1。CTHRC 1是一种分泌性蛋白质，其N-末端具有16个氨基酸的前肽。删除此 前肽增加蛋白质的生物活性。我们最近的研究结果表明， CTHRC 1的截短形式促进内皮细胞中的糖酵解，截短形式特别是 很有力尽管这些最初的结构-活性观察突出了蛋白质修饰的重要性 在控制CTHRC 1的活性方面，没有进一步的研究探索CTHRC 1的结构和功能之间的关系。 CTHRC 1已完成。此外，CTHRC 1的特异性受体仍然未知。在这 合作项目，我们的目标是研究CTHRC 1的糖基化如何影响其与靶细胞的结合 以及它在调节能量代谢中的作用。我们还将跟踪内化CTHRC 1的细胞定位， 通过化学标记不同的氨基酸残基来阐明其作用位点。了解促糖酵解 CTHRC 1的作用有助于理解正在进行的组织中内皮细胞的功能， 修复.这项建议旨在将CTHRC 1发展成为一个有价值的工具，以更好地了解 在伤口愈合过程中激活内皮细胞。为了实现这一目标，我们将采取跨学科的 以生物医学研究中心的专业知识和资源为基础的团队科学方法 卓越（COBRE）由NIGMS在密西西比和缅因州支持。通过利用最先进的糖科学 技术，我们的目标是解决再生医学领域面临的挑战。

Project Summary Understanding tissue healing and protein expression after injury is crucial in regenerative medicine. The glycoprotein CTHRC1 plays a vital role in tissue repair, regulation of fat cell formation, and bone development. It is produced by activated fibroblasts and contributes to metabolic efficiency and the survival of endothelial cells, which maintain homeostasis and capillary networks during healing. However, abnormal CTHRC1 expression is observed in chronic inflammation as well as malignant growth. While glycosylation is essential for the proper functioning of many secreted proteins, we don't yet understand how glycosylation impacts the beneficial effects of CTHRC1. CTHRC1 is a secreted protein with a 16-amino acid pro-peptide at its N-terminus. Removing this pro-peptide increases the biological activity of the protein. Our recent findings indicate that both the full-length and truncated forms of CTHRC1 promote glycolysis in endothelial cells, with the truncated form being particularly potent. Even though these initial structure–activity observations highlight the importance of protein modifications in controlling activity of CTHRC1, no further studies exploring the relationship between structure and function of CTHRC1 have been conducted. Additionally, the specific receptor for CTHRC1 remains unknown. In this collaborative project, our goal is to investigate how glycosylation of CTHRC1 influences its binding to target cells and its role in regulating energy metabolism. We will also track the cellular localization of internalized CTHRC1 by chemically tagging different amino acid residues to elucidate its site of action. Understanding the pro-glycolytic effects of CTHRC1 is instrumental in comprehending the functioning of endothelial cells during ongoing tissue repair. This proposal aims to develop CTHRC1 into a valuable tool to better understand the characteristics of activated endothelial cells during wound healing. To accomplish this objective, we will adopt an interdisciplinary team-science approach that builds upon the expertise and resources of the Centers for Biomedical Research Excellence (COBRE) supported by NIGMS in Mississippi and Maine. By leveraging state-of-the-art glycoscience techniques, we aim to address the challenges faced in the field of regenerative medicine.